WinUAE has a great feature where game controllers can be completely redefined to perform almost any function. Not only can you redefine things like up/down/left/right on the controller by pressing the desired control in the mapping screen, you can map keyboard keys to the extra buttons. For example, many games used the Spacebar as a second button to handle various game options. WinUAE allows you to map virtually any key or emulator control to a controller button. So you can easily map the Spacebar to one of the controller buttons and have the equivalent of a two-button joystick. With today's fancy gamepads, you could probably map almost all the controls for a flight simulator onto the various buttons. Adding flexible joystick mapping would be a huge benefit to WinVICE users.
Something similar can be done with external programs such as Joy2Key, XPadder and Total Game Control, but it would be nice if you didn't have to start an external program every time you wanted to use extra buttons in a C64 game.
Note: I've tried the SDL version, which supposedly can do things like this, but I didn't care for the fact that it doesn't have any UI.