This can be done as early as Wall 4, when you unlock Cultists.

This strategy relies on the fact that Mana Multiplier does not apply to Cultist mana generation, but does apply to the amount of mana recouped when the Cultist is sacrificed.

Basically we're going to push as high as we can in Cultists to generate a ton of mana, then stack Mana Multiplier to sacrifice them for a huge return.

So as a rough guide you're going to want to push as high into Cultist as you can, preferably hitting (20). Then you're going to want to split points into Mana Amplification and Mind Sphere depending on what you have available.

When you start the run you'll want to spawn as many cultists as you can to start generating mana. Then go garden for a while or make yourself a sandwich. Nothing you can do now affects mana generation.

Once you/re ready to cash out (use the Charged Mana icon on the left to determine how much is built up), start charging your orb. If you crack it don't sweat it, it won't affect the charged mana. Keep going until you manage to get it to the 4th level at least. That stacked with your Mind Sphere should leave you with a 5x or higher multiplier. Now sacrifice your Cultists to cash in all that Mana!

This strategy is very simple. Reset your skills and max out your points in Soul Contract to get them as cheap as possible, then spend your hoard of Mana to push your souls as high as you can!