Tyson-Douglas without question. It was a shocking upset, as well as an emberrassment to Tyson (scrambling for his mouthpiece, looking dazed/confused).
It's also tough for me to watch to this day because this marked the beginning of the end for Tyson.
No other fight can compare to that. It actually is one of, if not the greatest upset in sports history, not just boxing.
Some other upsets that come to my mind:
Carlos Baldomir over Zab Judah. Baldomir was a 20-1 underdog. No one really saw Judah losing this fight.
Bernard Hopkins over Felix Trinidad. Looking back now it's not shocking at all, but at the time Felix was 40-0 and was considered P4P the best boxer alive. No one expected complete domination and knockout for Hopkins.
Hasim Rahman-Lennox Lewis, I. Pretty shocking to see Lennox Lewis get KTFO. A fight that won me $50. Unfortunately the rematch cost me $100