How many systems have you configured at one time in ES? Might be worth trying the ES forums to see if there is a known limit. I have about 15 and it seems fine fully scraped.
I suppose that could be it, I had about 20. Down to 16 now. I think I might have been overly fancy with having Turbografx 16, PC Engine, Turbo CD, and SuperGrafx separated. I might just join all those into one menu as well as the Game Boy and Game Boy Colour.
Can I add Mega CD games to the Megadrive list too?
Yep, Genplus GX isn’t as picky either as it also allows iso + cue + wav :) The audio emulation on Picodrive isn’t as good either. In other words, just use Genplus GX!