When Brock Lesnar Superplexed him from the top turnbuckle, and the ring collapsed (it was rigged that way, but STILL!....)
Done again with Mark Henry which was just as awesome, if not more awesome than the Brock Lesnar superplex.
And then there was his match with Shane McMahon, where he fell off the Titan Tron and fell more than thirty feet to the arena floor. Shane then proved to be just as ballsy as his old man by jumping down after him for the pinfall.
This narrowly beat out what could have been another crowning moment a few moments earlier, when Big Show hit Khali with a flawlessly executed running spear that allowed for an instant pin. Seeing someone as big as Show flying through the air like that was damned impressive.
How about being only the third man to hold the WWE, World Heavyweight and ECW Championships? (The first being Kane and the second being CM Punk).
Even better he is the first and only man to hold those and the WCW title.
Winning the Intercontinental Championship from Cody Rhodes at WrestleMania 28, his first ever solo win at Wrestlemania, and becoming the 12th Grand Slam Champion. Wrestlemania moment indeed!
Also he is the third man after Edge and Kurt Angle to have held all of the currently active titles.
Given that, due to some of the belts being permanently retired, there are only four active wrestlers left that could possibly accomplish the feat (those being The Undertaker, William Regal, Mark Henry, and R-Truth... yes, you read that right), all four of them are over 40 and the only one that works a full-time schedule is the least likely to do it (R-Truth, who needs a World and the IC title and has been largely a career midcarder), Show may well be the last one to accomplish the feat unless one of the retired titles is brought back or the rules are changed.
In 2002, he once threw Rey Mysterio about five rows into the audience, an impressive feat even though he was a heel.
Responding to chants of "You can't wrestle!" by chanting back in EXACTLY the same rhythm "I don't have to!"