Worst, yet most hilarious mission failure EVER!!! I've been replaying GTA IV. The mission "Hating the Haters" requires you to protect your old friend Bernie while on a jog through the park. Poor ol' Bernie ends up taking a baseball bat to the ribs from a homophobe and a chase pursues. There is an extremely small window of opportunity to take out the attacker if a gun is equipped before Bernie gets ambushed. If the player misses the shot, he will hop on a Vespa and take off, resulting in you having to steal another Vespa (one of three nearby) and give chase. Unfortunately for me the bike that I grabbed happened to belong to an NPC standing nearby. Due to the animation of Niko starting up the bike, the NPC was able to rip me off the bike and proceeded to beat me up. I tried to pull out a gun but the guy kept punching me so I ran off to grab the other. Once again, the guy caught me and hauled me off! During that time frame, Bernie's pursuer got away. I finally got the upper hand on the NPC that caused me such grief by knocking him to the ground and emptying an entire AK magazine into him! I felt a little insulted.
... FYI, I'm not psychotic...