Part of Frog's upsetting there was that he just beat Liquid Snake in a nail-biter...not all of us were confident Liquid and Master Chief were that close together. Frog also nearly snuck a Noble Nine-break in the next round too thanks to the sprite round against Solid. Frog's run deserves a mention for being as close/fun/unpredictable as it was, and Frog > MC best represents that.
Most anytime Master Chief loses is a viable pick for this topic -- board-shock is important in this, but I think if you have the prediction-numbers overall that can be a form of qualification too. Casuals have eaten it a bunch of times so not just any casual-loss should get a nomination here, right, this isn't just the Mt. Rushmore of GTA-losses...but I think Frog's run fits the bill enough here.
Sub-Zero > Master Chief fits the bill too, though I felt like the board thought that was more possible at the time even when the prediction-picks didn't align with that.
O P E R A T I O N O U S T :
Nominate SHEIK!
https://i.imgur.com/OpudFxm.jpg