Hard to say, some people get a constant 30fps and some chug along in the custom areas. Not entirely sure what makes the difference at the moment
Difference between this mod and something like Bruce Pack or Defpack is that NTTE has a lot more constantly-existing objects and constantly-running code, particularly in the custom areas. Plus Nuclear Throne Together is pretty darn slow in its code execution since mods need to be interpreted on the fly. NTT might get updated to run on Gamemaker Studio 2 at some point, which I've heard might speed things up?
If not already true, something else you could potentially try is making sure you don't have too much open in the background, I notice I get less lag when NTT is one of the only things open. Also I think it helps if your computer has been restarted somewhat recently, frees up stuff I guess
* also yeah water quality options probably won't do that much - they had a lot more impact earlier in the mod's development when the water effects used way more memory. Lots of optimizations since adding the sliders.
** also also the shader toggle is just for people whose computers don't support shaders, crashing the game