First and foremost. Your Chassis will not determine your over-all max speed, that is the engines job. The chassis is all about acceleration, stability, traction, turning for both wide and short.
So yeah pretty important.

Please keep in mind, this is a work in progess from a novice, so please let me know if I am mistaken and I will change stuff if needed. Thank you

So here is what all those confusing numbers about chassis are all about.

AxB/C Tail/Mid lift
A: How many wheels total
B: How many wheels are motorized
C: How many wheels turn (if there is no /C then it is only 2)

So what does Tag/Mid lift mean?
Tag lift means the back wheels can lift up, Mid lift means the middle axel of wheels can lift up. When a set of wheels are lifted they reduce stability for sharper turning. I will explain, but let me make a point about stability first.

Stability:
When I talk about stability, I don't just mean what might flip you or not. I am also referring to the tiny turns you might make at fast speeds. Ever go 90-120 and make a turn into the other lane? You might notice you need to correct yourself by turning the opposite way. That is also stability.

Tag lift:
Those wheels in the back give worse traction on dirt, compared to ones more towards the engine, so lifting them up will help. Nothing to really worry about unless you go off road, or drive through a town

Mid lift:
The middle wheels stop you from really tight turns, so lifting them up leaving the front and the back wheels there mean much tighter turns, then you can put them back down for stability

Gas tank and accessories:
Another thing to consider is the size of your gas tank which changes depending on the chassis. 4x2 has the largest tank. 6x2/4 and 6x2 midlift have the smallest tank. Everything else has a medium gas tank. This is a visual difference if you look at the sides when changing chassis. Also on some trucks, if you aren't using the 4x2, you can't have some side panels and accessories.

Here are the different types of chassis for sale (not counting mods)
4x2: Starter wheels. Really tight turns, but no stability. It is easy to flip.
6x2: Much more stable, but sacafices turning by a lot. No sharp turns now.
6x2/4: just as stable, with an extra set of wheels to help you turn.
6x2 Taglift: Great for dirt roads. a little worse turning then 6x2/4 when down.
6x2 Midlift: Switches between the 4x2 for tight turning, and 6x2/4 for stability. This is currently mislabeled, and should be 6x2/4 Midlift.
6x4: With another set of motorized wheels it is the best for acceleration, but equal to the 6x2 for turning.

Which is better?
It really is a matter of preference, but here are the leading 3.
6x2/4: Good turning and stable without having to worry about it.
6x2 Midlift: Great turning, but like a manual transmition you need to switch it around.
6x4: For the acceleration with only decent turning and stability. Remember you can't make sharp turns with this. So going through town is more difficult.

Thoughts on Acceleration.
Basically acceleration is how fast you can get up to speed from a dead stop. The Chassis of choice for a lot of people is the 6x4, and who can blame them? You will be able to get up to top speed so much faster even with a heavy cargo, not to mention have little trouble in the dirt. Just keep in mind it still doesn't affect top speed, so you might want the other two choices for stability over start up. If you are a crazy lane changing roadside driver, being able to thread the needle is more important then acceleration.

When to put it up?
Tag/Mid lift are great if you are the sort who likes a manual transmission, and you realize the advantages of one in the first place. (me I respect those that do, but I don't use it myself) So the question is, when should you put those wheels up? It is simple really. When you are going slow, or have to tightly turn under 40 kmh, have them up, especially in dirt, or town. When you get on the main road and are picking up speed, put them back down again for the stability.

But I thought the engine handled Acceleration?
Technically yes, a bigger badder engine will give you more Acceleration, but all that is useless unless it has a chassis full of wheels to go through. So your chassis will affect your acceleration.

Tightness.
So I decided to list them in order from tightest to not. This is NOT in order from best to worst because there are many other factors. I'm just listing the turning tightness.

"6x2 Tag lift up" has the tightest turn.
"4x2" and "6x2 Mid lift up" are a close second.
"6x2/4" and "6x2 Mid lift down" are average.
"6x2", "6x4", and "6x2 Tag lift down" are below average.

I really hope this guide helps, please let me know if I am missing anything. If this did help please rate it up. Thank you all.