I've been setting up my Emu's with an Xbox 360, & I have a few problems overall.
First, let me say that the controller works fine in MAME, MESS, Nestopia, Fusion, Daphne, NullDc, & Project64. My problems come from working with a frontend. Hyperspin doesn't support gamepads, so you have to use Joy2key to navigate the menu's. This isn't too big a problem, except when you're in the emulators, you may get additional keypresses (for example, if MAME sees Joystick Button1 & joy2key has that mapped to a key as well).
The main problem I have is with NullDC, which also doesn't support gamepads. So, joy2key would be necessary to run this emulator with this controller. It seemed like mapping all the keys ini joy2key would cause more keypress problems in the other emus. I suppose Chankast or Demul might solve the problem, but I haven't tried them yet...