L5R is already mentioned and I can support that choice.
Another good one I think is Alternity. Not for sale anymore unfortunately (except on e-bay and such-like), but it's a very customizable system. The basic settings are stardrive (SF) and dark matter (X-files like contemporary setting), but the system is very versatile so you can do about anything with it. Also quite deadly (realistic as one pistol shot can easily kill your character) but the idea is to finesse your way to a solution and not battle your way there.
I've also played D&D, Vampire dark ages (old WOD), Mage (new WOD), Deathwatch, Exalted, Star Wars (D6 as I don't like the D20 system), Star Trek and many more. I think that you can do just about anything, as long as you and your group agree.