Honestly, my biggest disappointment in gaming was Phantasy Star Online. I adored the old Phantasy Star games, they were fun, epic, worked well... And Online just felt awkward as hell and dull. The redone version for the GC was a little better, but still sadly lacking. (Universe is a giant step up, but still not as good as the old games.)
Second biggest, in all honesty, was Final Fantasy 12. I played about halfway through the game, and finally simply gave up. Perhaps one of the most boring games I've played. I kept waiting for the story to really start, and it just wasn't there. The gameplay also, overall, felt weaker than hell. Seriously, when I can simply turn on a couple gambits and set back and watch everything die, there's something wrong. And the cast was dull, annoying, or forgettable. And I should note, I love FF. Have for a long time.