My own favorites:
Wing Commander: Definitely kick-ass. Not to mention WC3 and 4 are excellent examples of how to do FMV right, and gave me renewed appreciation of Mark Hamill, Malcolm McDowell, and John Rhys-Davies.
Civilization: The original is a classic, and Alpha Centauri is a fabulous SF "update" that drips with atmosphere.
Fallout: Great kitschy humor combined with some serious SF-themed moral dilemmas. I too am looking forward to seeing how Fallout 3 shapes up.
StarTropics: How can you not love a game series with a redheaded be-freckled teenager who goes around tropical islands throwing yo-yos at mutant slugs, sticking bananas in his ears, and dressing up as a woman, while trying to save his uncle from space aliens? And then, later, gets to travel around time doing such things as delivering pizza to Cleopatra and collecting magical Tetris pieces?
Peace & Luv, Liz