Top 2 for me as noted above are UCONN/Mississippi State and Baylor/Louisville. Other games that were very unexpected:
2016: 3/4 of the #1 seeds go down in the Sweet 16 or Elite 8. Notre Dame/South Carolina both had incredible seasons losing just 1 game to UCONN in the regular season and seemed like locks to make the Final Four. Notre Dame lost to a relatively underwhelming Stanford team that tournament and South Carolina unexpectedly lost to Syracuse. Then you had Baylor as the 4th #1 seed who was 36-1 and they lost in front of a home crowd to Oregon State in the Elite 8. Going into that tournament it seemed like a given all of the #1 seeds would make the final weekend but only UCONN got there.
2023: #1 seeds Indiana and Stanford lose at home. Indiana especially was shocking for me considering how great they'd been all year. Stanford had signs of disaster but that was also very unexpected.
2023 Iowa beating South Carolina. Probably my #3 or 4 upset all time. Everyone was intrigued to see how Iowa would do but very few people thought they had a prayer to pull it off considering how much bigger and more athletic South Carolina was. One of the better games in NCAA history.
2011: Notre Dame beating Tennessee and then UCONN en route to the title. I think that's the only time a team beat both Pat Summitt and Geno in the same tournament. Notre Dame had lost something like 25 straight games to Tennessee and Tennessee had a fantastic team that year who was 34-2 and had won 25 straight games. They were the clear favorite but Skylar Diggins torched them. Then in the Final Four Notre Dame faced UCONN it was Maya Moore's senior year. Notre Dame had lost 3x to UCONN that year and hadn't beat UCONN in years. All signs pointed to UCONN winning their 3rd title but Diggins stole the show again and pulled off the upset. Baylor losing to Texas A&M in the Elite 8 was also a major upset that season after they had owned A&M earlier that year and looked like a major title contender.
2007: Rutgers beating #1 Duke in the Sweet 16. Duke had an undefeated regular season and had beat Rutgers by 40 points earlier in the year. Lindsey Harding missing 2 free throws down by 1 point with less than a second left on the clock to lose the game and end her career had to be the most brutal ending I've ever seen for a player.
2004: Minnesota beating Duke in the Elite 8 and ending Alana Beard's career. I think most were hyped up for a Beard/Taurasi meetup in the Final Four, Duke looked primed to make a championship run in Beard's final year with a very talented squad but Whalen/McCarville carried Minnesota to a semi-Cinderella Final Four. Minnesota was the 7 seed but dropped significantly due to Whalen missing a lot of time with injury.
2001: Xavier clobbers Tennessee in the Sweet 16. Tennessee lost Catchings midyear but still had a great team and dominated a very strong SEC (and beat full strength UCONN at home) without Catchings. Losing in the Sweet 16 to Xavier of all teams came out of nowhere.
Also #5 Southwest Missouri State handily beating #1 Duke in the Sweet 16. I don't think this was necessarily the biggest upset but there was a magnitude about it with all time leading scorer Jackie Stiles leading an underrated team past the favored #1 seed.
1999: Duke upsets Tennessee in Elite 8. Most had Tennessee penciled in for a championship matchup with Purdue as they were viewed as the top 2 teams all year. Tennessee had Chamique Holdsclaw as a senior and most thought she'd close her career with a 4th title but Duke played great while Tennessee had one of its worst showings on the year.
1998 Texas Tech as a 1 seed loses in the 2nd round by 15 at home to Notre Dame. I don't know much about Texas Tech's team but they were 25-4 entering the tournament.
