The single worst performance I ever got out of anyone was 2004 Ryan Drese in a single-season prog. I had a contending team, was certain we'd make the playoffs, but lost the division by 2 games and the wild card by 1. Drese was my #3 starter and he sunk us.
Real life stats: 208 IP, 14-10, ERC+ 106, ERC# 3.97
Sim stats: 198 IP, 6-17, 9.00 ERA
Never used him tired, and he had a conservative pitch count. Couldn't figure out why he performed like a 200K mop all season when he had slightly better than league average normalized numbers.