I'd say maybe GER from Part 5, mostly because of the fact that Return To Zero would make Goku's attacks against Giorno useless, and also could psychologically destroy Goku from the fact that he'll keep dying and never reach his true death.

From the simple fact alone that it was powerful enough to counter King Crimson's Reality and make it his own world where we had the complete power could be devastating to Goku, its a point of no return, where not even Dragon Balls could even to the simple thing of saving him.

Then, there's also the Saitama argument, and also bringing up Kars.