52 buttons and 16 axis. Thats gonna be pretty intense man. (heck i have a steel battalion controller that i wired to arduino, and thats only got like 9 axes, and like 40 buttons) Though that didnt get plugged into a PC.
A far as getting your joystick and button readings, those are pretty straightforward
Might be a bit helpful if you haven't played with a joystick yet.
http://code.google.com/p/unojoy/wiki/GettingStarted
These guys have made a library that will let an arduino act as a USB controller to plug into a PC. I haven't messed with it (though it looks like I'm going to this weekend) and will probably be about what your looking for. As far as having all those switches is concerned. You might wanna start with maybe 2 axis, and like 6 buttons. Then add more as you get them all working, and make sure they work on your computer.
Edit: Now that i look at their page a bt more and how they get the program to work. i think it might not work on a mega since they're redoing some of the code in the bootloader with the intent of it being on an uno. Though depending on what your doing. You might not need more then an uno, if you get creative.