You guys are all far too America-centric, try to broaden your sporting horizons a little, eh?
In terms of recent events, yeah, Greece winning Euro 2004 and Liverpool coming back from 3-0 down against AC Milan were pretty big, I must say. My favourite, though, comes from a lot closer to home, and that is Munster's 12-0 defeat of the All Blacks on the 31st of October 1978 (that'll be New Zealand being beaten by an Irish province in rugby to all you ignorami out there). To really appreciate it though, you have to understand the context of the victory, it's not just that the All Blacks were favourites to win the match, it's that the All Blacks would have been favourites to win any match, against team they could possibly have come up against. They were on the very last match of a tour which had not only seen them beat the best teams in Europe, but not even concede a single try while doing so. The second best team in the world beating them would have been a huge upset. But Munster were definately not the second best team in the world, far from it. A local provincial side entirely comprised of amatuer players (one of the 15 was a butcher who now lives across the road from a friend of mine, another is a work colleague of my father's, just to illustrate how local this team really was), who were not only many leagues away from their New Zealand counterparts, but had been going through a patch of poor performances lately to boot, were up against what was seen as one of the best squads of 15 the sport had ever seen. To have expected Munster to actually win on that day would have been unfathomable, it wasn't simply against-the-odds, it was beyond any chance or hope that a Munster fan could have possibly had in the game. Yet they did it, they actually went on to beat the best team in the world without conceding a single point, and it wasn't just to win a trophy or get to the next round of a competition, it was simply because they could, and they showed us all that on that last day of October in 1978.
And that's my suggestion for the greatest sporting upset in living memory.