Hands down, Indiana Jones and the Fate of Atlantis. It was a game I could put down and then go back to two years later and still enjoy it. Excellent graphics, sound, storyline was interesting, locations were cool, and the replay value was phenomenal. You could choose between thinking, fighting, or team playing which all lead to different game play, different outcomes, and even some major changes in the storyline. It was also one of the few games that I've played that I felt, could only be played on the computer and be fun. If I had to click through things with an Xbox or Playstation it would suck. Maybe I'd play it on DS, but that's it.
Intro: Indiana Jones and the Fate of Atlantis
Honorable mentions: The Sims 2, The Sims: Hot Date (solely for that crackhead of an old lady who would some how always show up as you're getting frisky with your date), Maniac Manson, Full Throttle, Quake III Arena, Sam & Max Hit the Road, and Day of the Tentacle.