Seems to be limited to the SNES.  Games like Super Mario RPG and another that was a Tetris/Dr Mario combo both say to detach the multiplayer adapter.  I'm only using a single usb SNES controller.  RP2 with 4.0.0 Beta 2.

Some games I've noticed seem to believe that there is a multiplayer adapter attached.  This prevents the games from being played.  I would like to disable every controller but 2.  I'm not sure if this would allow the games to work but it potentially could.