Some of the following tips are pretty straightforward, if you already knew them please go on reading, but don't insult me in the comments (it already happened many times on payday 2). Thanks and have fun reading and playing. I hope it will be useful.

• Tip #1:
  Before taking off, lock your pilot to his seat, so you won't accidentally move him around and, well... risk to crash your bomber.
  
• Tip #2:
  There are some useful pre-made hotkeys you can use:
  "ctrl" will slow down time for a little bit;
  "R" will force the selected crew member to go to the ammo box and reload his ammo;
  "F" will force the selected crew member to go to the medbed (both of them won't work on the pilot if he or she is locked to his/her seat);
  "P" will force the selected crew member to go piloting the bomber (only available if no one is already on the pilot seat);
  the "1-7" keys (not the numpad ones, the ones above your main keyboard; "1-9" in the USA AF DLC) will make it easier to control every single crew member without the need to select him directly with the mouse or in the left menu;
  holding down "SHIFT" will zoom inside the bomber until you release, then the zoom will reset to the one you had before pressing the key.
  
• Tip #3:
  try having always at least one parachute on board, it will come in handy if you need to repair an engine mid flight. Order your mechanic to take it before you tell him/her to go outside and repair the engine, so if something goes wrong (in my personal case I killed one because of an emergency dive) he can have a chance to be saved.
  
• Tip #4:
  If you are above the UK land the crew members will always be safe even if they bailed out or you performed an emergency landing.
  
• Tip #5:
  If some of the crew members get injured (they are down and timer before they die shows), but you are about to land at the airfield they will survive even if you don't help them with a medikit.
  
• Tip #6:
  Don't upgrade everything in the bomber as soon as upgrades are unlocked. Many upgrades are close to each other in terms of intel points, so it's better to wait and do one or two more flights and get the required points and money to upgrade to something more powerful.
  
• Tip #7:
  Buy the engine extinguishers as soon as possible, even if they have one charge they are far from useless considering the only other way to put out a light engine is to perform an emergency dive, which requires at least mid altitude and before you reach it and perform the maneuver the engine will most likely be broken and will need mid flight repair.
  
• Tip #8
  Don't be a dummy like I am, use the evasive maneuvers after you unlocked them. A well timed "evade flak" or "corkscrew" will avoid you much unnecessary damage to the bomber and even the crew.
  
• Tip #9:
  Again, don't be a dummy like me, remember to use mechanic's "lean" and "boost", they save the day in most of the cases.
  
• Tip #10:
  Radio Op has the "autotag" skill, useful right before a bomb run. It will last for only some seconds, but while you are busy aiming your target it can save you by tagging all the enemies in range. My tip is to activate it right before you start the bombing procedure (opening the bomb bay doors, aiming and dropping the bomb) to maximize its effect. Furthermore, don't count too much on it, the cooldown is massive for the pace of this game.
  
• Tip #11:
  Remaining on the Radio Op topic, try to time the spitfire call to maximize its effects. My advice is to activate it when you are at approximately 1 minute from your target (you can read the time on the right of the navigator menu, under E.T.A.). Even this skill has a massive cooldown (longer than the autotag).
  
• Tip #12:
  The navigator custom markers are a massive help in some missions, especially if you need to avoid radar equipment or you want a recon photo for some extra money. They will be purple on the UI and are pretty visible.
  
• Tip #13:
  Try to always combine gunners' skills because they are more effective. If you have special ammo types, try to always combine them with focus, they will result in a constant stream of projectiles towards enemies (due to the non-depleting nature of special ammo they won't require reloading).
  
• Tip #14:
  Always, and I mean ALWAYS, train the bomb aimer to be a gunner as secondary skill.
  
• Tip #15:
  Use high altitude only if you really need it, your crew will be hevily affected by the low temperature.
  
• Tip #16:
  Don't go at high altitude if your crew doesn't have oxygen tanks. While they are in their seats nothing will happen, but as soon as someone leaves the seat, the oxygen timer will kick in and it usually lasts for only a couple of seconds without oxygen support. Furthermore if your oxygen tank breaks, the mechanic is needed to repair it manually and in the meanwhile the rest of the crew won't receive oxygen at their seats.
  
• Tip #17:
  Buy the ventral turret around mid game (if possible even earlier). There's a type of enemy (the big white fighters) which has a hard-hitting attack pattern, it will position beneath the bomber and will try to shoot inside the bomb dock to make you blow up. The ventral turret is almost the only solution to deal with it (unless you want to take the risk of opening your bomb dock and release a bomb on it).
  
• Tip #18:
  If you are low on money prioritise upgrading first the front, main rear and tail of your fuselage, leaving the others behind. This way you can ensure your gunners and pilot are the most protected.
  
• Tip #18:
  Armoured engines are quite good if you don't want to see them while they fall, but they decrease the weight limit, so I personally don't reccomend them.
  
• Tip #19:
  Ammo feed turrets are game changer, allowing one less task for the player to focus on. The first one you should buy is definitely the rear one, leaving the mid upper and ventral for last since they have the ammo box right near them.
  
• Tip #20:
  Buy the electrical and hydraulic mk2 systems as soon as you can. My personal experience both in RAF and USA AF are full of breakdowns in the middle of the combat, and without electricity your radar won't work, without hydraulics, your turrets won't be able to rotate.
  
• Tip #21:
  If you are low on money, don't waste them buying better fuel tanks. Tanks damage are so rare that when one happens is faster to order your mechanic to transfer all the fuel in the other tank using the pump.
  
• Tip #22:
  As soon as you can, buy the front equipment rack and set it to have at least one fire extinguisher. I say the front one because if a fire starts during a combat, the only crew member you won't need is the mechanic, so you can tell him to take the extinguisher and he/she will do it faster because it's right near his/her seat.
  
• Tip #23:
  To avoid having weak crew members, try to use one (I personally use the mechanic) as a jack of all trades. This way you'll have to focus on one person while all the others are well protected and armoured.
  
• Tip #24:
  If you have the secret weapons DLC, give all your crew the thermal flightsuit 3. It will massively rise their cold resistance.
  
• Tip #25:
  Try using the secondary skill to complement your crew members (more on this in the "Crew setup" section).
  
• Tip #26:
  Before you take off, arm a bomb, so you don't have to do it in mid flight at least for one target).
  
• Tip #27:
  When performing an emergency landing with less than 2 wheels, hit the "Emergency land" button on the pilot GUI.

In this section you will find useful (I hope) informations on how to manage your crew and their gear. (the stats values are taken from my crew and may differ a bit based on the starting values of your specific crew member).
The pilot doesn't move very much. It's important to ensure he's safe at any given time. With this setup he/she will get (when using the specific equipment written down below), the following stats: 68 armour, 42% speed, 77 thermal resistance, 1:10 minutes of oxygen.
Gear:

• Thermal flightsuit if you own the secret weapons DLC or the one you prefer if you don't own it.
  
• Progressively better helmet as you unlock them. Go up to the flak helmet mk2.
  
• Advanced O2 bottle, or anyone until you unlock it apart from the toughened ones because they reduce the oxygen timer.
  
• Progressively better flak vests, up to the heavy flak vest mk3.
  
• Leather or toughened leather gloves until you unlock the electrically heated ones.
  
• Leather and toughened leather boots until you unlock electrically heated ones.

The mechanic is the most moving crew member, roaming in and out the bomber to repair stuff. He needs a lot of movement speed. With this setup he/she will have: 43 armour, 70% movement speed, 49 thermal resistance, 1:10 minues of oxygen).
Gear:

• Thermal flightsuit if you own the secret weapons DLC or the one you prefer if you don't own it.
  
• Service cap.
  
• Advanced O2 bottle, or anyone until you unlock it apart from the toughened ones
  
• Progressively better flak vests, up to the heavy flak vest mk3.
  
• Fingerless woollen gloves.
  
• Plimsolls until you reach electrically heated boots.

The navigator doesn't move much (unless you train him/her to be a mechanic), so this gear should keep him safe. With this setup he/she will have the following stats: 67 armour, 42% movement speed, 67 thermal resistance, 1:10 minutes of oxygen.
Gear:

• Thermal flightsuit if you own the secret weapons DLC or the one you prefer if you don't own it.
  
• Progressively better helmet as you unlock them. Go up to the flak helmet mk2.
  
• Advanced O2 bottle, or anyone until you unlock it apart from the toughened ones.
  
• Progressively better flak vests, up to the heavy flak vest mk3.
  
• Leather or toughened leather gloves until you unlock the electrically heated ones.
  
• Leather and toughened leather boots until you unlock electrically heated ones.

As before, he/she won't move very much, so I'm using the same gear as the navigator. With this setup he/she will have the following stats: 67 armour, 42% movement speed, 67 thermal resistance, 1:10 minutes of oxygen.
Gear:

• Thermal flightsuit if you own the secret weapons DLC or the one you prefer if you don't own it.
  
• Progressively better helmet as you unlock them. Go up to the flak helmet mk2.
  
• Advanced O2 bottle, or anyone until you unlock it apart from the toughened ones.
  
• Progressively better flak vests, up to the heavy flak vest mk3.
  
• Leather or toughened leather gloves until you unlock the electrically heated ones.
  
• Leather and toughened leather boots until you unlock electrically heated ones.

I'm using the same gear for all of them, in order to make them like a fortress. They will have the following stats: 83 armor, 40% movement speed, 27 thermal resistance, 50 seconds of oxygen. The movement speed might seem to be very low, but when you reach the same gear as featured here you will most likely have every single turret as an ammo feed one, so there's no need for them to move back and forth to reload their ammo.
Gear:

• Thermal flightsuit if you own the secret weapons DLC or the one you prefer if you don't own it.
  
• Progressively better helmet as you unlock them. Go up to the flak helmet mk2.
  
• Toughened large O2 bottle, or anyone until you unlock it.
  
• Progressively better flak vests, up to the heavy flak vest mk3.
  
• Leather and toughened leather gloves.
  
• Leather and toughened leather boots.

Here I will show my personal choices for the crew training and why I made them. Many of them will be an implementation to work as pairs.
Train the pilot to be a mechanic as secondary. This will make sense in a moment.
Train him/her to be a pilot. If the enemies shoot down the pilot having a backup is always useful, and having it right next to the pilot seat is even better. As soon as your pilot goes down, order the mechanic to switch seat and take control of the bomber. Then use another crew member to revive the pilot and send him/her to heal. After he/she is completely healed send him/her to the mechanic seat, so you don't have to switch them back mid flight and you can have fuel situation, pumps and mixtures anyway.
Since they are close to one another, train them to take each other's place if needed. Your navigator will also be a radio op and the radio op will be a navigator. This is especially useful if one of them is downed and/or needs meds. You can send him/her to the medbed and switch back and forth between the two equipments (maps and radio) with the other one.
I personally use one of the gunner as a mechanic, due to the fact that some systems are near the bomber tail, the tailgunner is perfect for this job. The other gunner (the mid one) is trained to be a first aid medic. I made this choice because the tailgunner is very slow and it's faster to leave him/her at the gun turret while moving the mid gunner to the back and heal the dude than moving the tailgunner himself to the medbed.
Obviously trained to be a gunner since a turret is just above the bomb aiming cupola.

In this section I'll give some tips for the bomber to make it a flying fortress.
The engines are the most important part of the bomber, without them you can't fly (obviously), but there's more. They also allow for more equipment to be carried around due to their weight limit increaser nature. My personal tip is to use a hybrid setup,with two standard engines (personally the outer ones), and two lightweighted engines (the inner ones). This way you can maximize weight (with two standard mk5 and two lightweight mk3 the weight limit is 10000) and still have some protection on half of your engines (the lightweight have very low armor). In my personal experience I never used the armored engines because they reduce weight limit too much for my equipment.
Since there are very many gun turrets to choose from, my advice is to not buy every single one that comes out, but one every two or three unlocked. If possible, buy the ammo fed ones, so you don't have to manage your gunnners' reload. When around mid game or a bit earlier, buy the ventral turret. It will be helpful against those enemy fighters that place beneath the bomber to shoot bombs. If you are low on money or close to the weight limit, leave the nose turret upgrades for last since the front gunner is also the bomb aimer, he/she will be the less shooting one in most cases.
Some of the systems are too useful to be left unupgraded. If you ask me which systems are the crucial ones, my answer will be "electrical, hydraulics and radar". For electrical and hydraulics, buy the mk2 upgrade as soon as possible, due to the increased reliability. The radar upgrades are mainly for the reduced sweep time. It may not seem a good upgrade, but from mk1 to mk2 the 2 seconds reduction is a massive help in early stages.
The other systems need upgrades too, so if you don't know which prioritise, my advice is to upgrade extinguishers first. Oxygen system and tanks are not that important.
Since at the start you will only have the two back equipment racks, I reccomend to buy the other two before going on with the upgrades. Start with the front one and put a fire extinguisher in it as first equipment. In the rear and mid rear racks I reccomend having at least one medikit. When you upgrade the racks, having one parachute in the front one is always useful. With full upgraded racks I personally have one medikit for every single crew member, for a total of seven medikits scattered around the bomber.
The fuselage depends heavily on your playstyle. Mine is all armoured of the best kind for best crew protection. As I already wrote in a tip at the start of this guide, the best choice is to upgrade first the fuselage parts where the key crew members are located, so prioritise front, main rear and tail. After you upgraded these ones, go on with the other pieces.
This compartment is the one I most neglect, but I have some tips anyway. If you are playing the main RAF campaigns, it's better to upgrade the homig pigeon, due to the nature of the map. You have missions mainly above the continental Europe and the only sea you see is the English Channel. On the other hand, if you are playing USA AF DLC it's better to upgrade the dinghy, since most of your flights will be over the Mediterranean Sea.
In my best bomber (aka the one with which I finished the game), I have the following setup:

• Engines: standard mk5 on port and starboard outer; lightweight mk3 on port and starboard inner
  
• Gun turrets: .50x4 + ammo feed on every single one; I own the secret weapons DLC, I installed two homing missiles too (if you don't have the DLC it won't make much difference)
  
• Systems: electrical mk5, hydraulics mk4, radar mk5, engine extinguishers mk4, oxygen tank mk3, self-sealing fuel tanks
  
• Equipment: 3 slot racks everywhere with the following equipment: 3 parachutes on the rear, 3 medikits on the mid-rear and mid-front, one of each equipment on the front one
  
• Fuselage: armoured fuselage mk7 everywhere
  
• Survival: inflatable dinghy mk1 and homing pigeon mk3

This was a pretty long guide, if you managed to read everything, a big thank you for your time. It required a lot of time to make everything (especially for me to remember every single one of the tips). I probably forgot something, if so, I will update as soon as I remind.

One wheel landing and belly landing

Here you can find the various guide updates when they come out.

-16/02/2020: Added tip #27; thanks to the suggestion from a comment under my "How to land with one wheel or no wheels" guide.