In terms of settings, you won't need to tinker with many for any of the emulators. If you're into cool overlays and shaders that mimic playing on old CRT TV's or handhelds, then I recommend downloading and running
Floob's video manager script. It will auto-apply some really cool overlays and shaders to all of the appropriate systems, and I think that they all look fantastic.
Otherwise all controls are already configured automatically thanks to Retroarch, so any other tweaking that you might want to do will be highly dependent on your personal tastes.
See my post a little ways up this page about some settings you can change to eliminate input lag as well.