If any difficulty under "bring it on" gets chosen in the settings-menu, the game will fail to load mods after restart.
following error is displayed:
Failed to load mods: Error while loading recipe prototype "omega-armor" (recipe): Value (72088) outside of range. The Data type allows values from 0 to 65535 in property tree at ROOT.recipe.omega-armor.ingredients[0].amount
Modifications: Thech tree plus.

Im using Tech tree plus in version 1.6.6 as the only loaded mod alongside Elevated Rails, Quality and Space Age.
All settings are on default except for the difficulty.
The Settings: Bring it on, don't destroy my base please, Can I craft engineer and Pyanodon ist too tuff? are working fine.
Every option below "Bring it on" will lead to the Error above.

Also sidenote, is it on purpose that on the difficulties "don't destroy my base please", "Can I craft engineer" and "Pyanodon ist too tuff?" the Quality Modules have negative Quality modifiers and dont scale with Quality?
On "Bring it on" they work as intended

Thank you for shedding light on this.

It has nothing to do with other mods, the issue is that factorio only allows ingredients in recipes to have a max amount of 2^16 - 1, anything more and it will crash the game. That is why the Omega armor has 65535 baked right into it and it is on me that I have neglected the difficulty interaction.

The quality having negative quality modifier is a typo on my part. I accidentally did not change speed to quality when expanding upon it.

Fixed in 1.6.7

Thanks for the quick fix.
Can confirm that difficulty is fixed.

Speed Modules and Quality Modules now also have the correct set of modifiers, even with many mods enabled. ^^