Most of the big upsets since 1990 are probably little remembered now, but here's a general rundown, with most involving #1 seeds. The biggest upset ever would have to involve at least a #1 seed, but there have been early exits by #2 seeds that were at least a bit of a shock. One not listed is the aforementioned loss by undefeated UConn team to UTenn in the 4th round in 1997. That team had won the BET at home by only 9 over an Irish team they had earlier beaten by 23, and the Huskies' 5-point margin over Illinois in the Sweet 16 game was the smallest of all the winners. Writing may have been on the wall there for the Huskies.
1991 - James Madison beats #1 seed PSU in 2nd round (first game for Lions).
1992 - SW Mizzoo beats #1 seed Iowa in 2nd round (Hawkeyes' first game), and goes on to beat #2 seed Mississippi in the 4th round.
1993 - SW Mizzoo beats #2 seed Maryland in 2nd round (Terps' first game), Colorado beats #1 seed Stanford in 3rd round.
1994 - LA Tech beat #1 seed UTenn in 3rd round.
1995 - Purdue beats #1 seed Vandy in 3rd round.
1996 - George Washington beats #1 seed UNC in 3rd round.
1998 - NC St. beats #1 seed ODU in 3rd round, #9 seed Notre Dame beats #1 seed Texas Tech in 2nd round, #16 seed Harvard beats #1 Stanford in 1st round. Year of upsets.
1999 - Duke beats #1 seed and reigning champ UTenn in 3rd round, Iowa St. beats #1 seed UConn in 3rd round.
2001 - Xavier over #1 seed UTenn by 15 in 3rd round. SW Mizzoo over #1 seed Duke in 3rd round sets up a 5-seed vs. 6-seed battle in regional final.
2004 - #7 seed Minnesota over #2 seed KSU in round of 32 sets up meeting and victory over #1 seed Duke in regional final.
2006 - BC over #1 OSU in 2nd round.
2007 - UMiss beats #2 seed and reigning champ MD in 2nd round, Rutgers beats # 1 Duke in 3rd round.
2009 - MSU beats #1 seed Duke in 2nd round, Louisville wins by 17 over #1 seed MD in 4th round.
2010 - Baylor beats #1 seed UTenn by 15 in 3rd round, KY beats #1 seed Nebraska in 3rd round.
2011 - #11 seed Gonzaga uses home court advantage to knock off #3 UCLA in 2nd round and advances to play Stanford in regional final.
Louisville over Baylor in 2013 still seems much bigger than all the games where #1 seeds were eliminated in the 2nd round. Harvard of course still has the magic game, though injuries set it up.