You can do it in Joy2Key, but switching between profiles is a challenge. I highly recommend one of 2 other options. 1) You could use XPadder instead. This program does everything Joy2Key does and much more. It is also in active development, so you could ask the author questions or request features if desired. It has a command line interface, and it's EASY to switch profiles in a single command. This is the most robust solution and possibly the easiest. 2) You could use the built-in joystick remapping capability in GameEx. This will allow you to set up different configurations for each emulator and it will do everything for you when running. Since it's built-in, there should be no extra system resources tied up like you might see with XPadder or Joy2Key. If you are really, really attached to Joy2Key for some reason, there is a thread from a long time back that discusses a way to make Joy2Key work, but it involves changes to the registry for each run. Not really a problem, but definitely not the best solution.