It supports an unlimited number of emulators, although it currently only has 3D modelling for some of them (portables like the GBA/Lynx in particular require individual models, but I'm trying to make an easy way to import your own).
Currently all other emulators default to using the Sega Master System layout (TV & tall box).
Emulator/collection configuration is pretty straight-forward. You can add emulators through XML files (I have files for a dozen different emulator setups left over from when I was making EMUCenter, the frontend for Media Center).
You then simply choose where the emulator is installed. If the emulator only supports one system it then tries to find the ROM path, if it finds the ROM path it will then try to find the snapshot, movie and title folders to suit. (if it can't automatically find any of these it will ask you for them). If the emulator supports multiple systems like KEGA Fusion does, you can specify individual ROM paths.
It then goes through the ROM folder, removes all of the goodtools naming from your ROMS and adds them to the collection.
If you've got everything set up relatively well and all of your images downloaded, you really only have to the one thing to set up the emulator - choose the game path. If there's a ROMS, SNAPS and MOVIES folder underneath the emulator, everything else will be handled automatically.
MAME is the only difference - in its case, I actually run MAME with '-verifyroms' to ensure that only working games are listed. It takes a while, but it's worth the time.