Well, two slightly less well known games that I've either run or been a part of that were rather fun was Fading Suns and Rogue Trader.

Fading Suns can be seen sort of as a less grimdark Warhammer 40k meets Call of Cthulhu. Essentially, it's fantasy kitchen sink/Space Opera setting that uses a blackjack style rolling system to determine success. It has one of the most flushed out martial arts combat section I have ever seen in a game like this, even more so considering that the technology get to psychic weaponry. I'd give it a look through, especially since a new edition is supposed to be on the horizion.

If you're familiar with Dark Heresy, you probably have heard of Rogue Trader, or at the very least, you know the setting. Instead of being Acolytes doing the dirty work for your Inquisitor, you and your buddies/future victims/backstabbers are merchants trying to make a fortune. This one is definitely more of a player vs player sort of game, but it ends up being a ton of fun, most of the time.

Of course, I'll throw in a few setting that everyone should at least take a look at; Deadlands and Weird Wars, which, if memory serves right, have materials for D20, Savage Worlds, and Gurps. Take a look at these if you want to run some sort of alternate history game.