When he destroyed the Potara earrings.
Majin Buu (who was only revived due to Vegeta's stupidity) is kicking the crap out of everything that's thrown at him. He's already defeated Gotenks and Mystic Gohan, and is just getting stronger with each battle. Goku, in a last ditch effort, has been given a powerful artifact by Elder Kai - the Potara earrings. The earrings will fuse any two fighters together, multiplying their fighting strength. He manages to convince Vegeta to fuse with him, but the two are absorbed by Buu following a short battle. Inside Buu, the fusion is nullified, and Vegeta, rather than saving the earring for when they get out of the pink monster, so they can re-fuse and finally put an end to him, destroys it.
When they get out of Buu, he proceeds to wipe the floor with Vegeta's dumb ass (I'm sensing a pattern here).