The hardest game I've ever played was probably Harry Potter and the Deathly Hallows Part 1. I managed to beat it on Easy mode, but only just barely.
On the other hand, Terraria on Hardcore Master GFB would probably be worse. I've never played Terraria on that high a difficulty though or watched someone do so.
EDIT: I just looked at page 1 and saw someone mention Super Ghouls and Ghosts, and I've played that. It's DEFINITELY HARDER.
Super Punch Out! might be harder though, I'm not sure which is harder since I've barely made any progress on either one.