4. All of Them (Dead Island)
Ya know, it may be a little unfair - your average person would be so terrified at the prospect of an actual zombie uprising, they probably would be pretty helpless if you tried to lead them to safety during an undead apocalypse. Doesn't matter whether it's in a mall or a tropical island - people just aren't equipped to deal with it, emotionally or mentally. Still, that doesn't make it any less frustrating to see an NPC stop dead in their tracks while a horde of zombies descend on them for practically no reason, then decide to run at the zombies, or wander off-route entirely while you desperately try to keep the hands of the newly-risen off their fragile, vacation-tanned skin.
3. That Fucking Nuke Truck (Blast Corps)
I'm not sure if it's ever given a proper name, but that's not important, because everyone who played Blast Corps will probably recognize it by "that fucking nuke truck" - the truck that drove in a relentless straight line at the same speed, regardless of what was in front of it or the fact it was carrying some EXTREMELY sensitive nuclear missiles. You're stuck in a variety of vehicles to destroy all of the buildings and obstacles that the fucking nuke truck might run into, while unable to just - I dunno - turn on the thing's parking brake or give it some flat tires or ANYTHING that would stop it from ramming into danger for no reason. The end result is that you have to destroy pretty much every building on Earth in order to save everyone on Earth, often using incredibly dumb vehicles (lookin' at you, Backlash) to get the job done. Frankly, if humanity's dumb enough to unleash a fucking nuke truck on a set path and then realize WITH SECONDS TO GO that, oh yeah, better get rid of those buildings, maybe they deserve a nuclear winter.
2. The Alchemist (Spyro 2: Ripto's Rage)
The only good thing about the Alchemist escort mission in Spyro 2 is that it's optional. Because other than that, it's a laundry list of everything that can possibly be wrong with escort missions. The Alchemist - who must be pretty smart to have invented some magic potion - stumbles directly through a field of unkillable rock monsters without slowing down at any point, forcing you to run back and forth, trying to knock said rock monsters onto their rock-asses long enough for the dopey Alchemist to bumble through. That Alchemist guy, by the way? Dies after one hit. None of this would be unforgivable, except he takes the most circuitous path possible to get to his end destination - going past every single individual enemy to get to a spot that was about 20 feet away. And what do you get as a reward? Another orb. Makes you miss the days that dragons would spend their time burning down villages and terrorizing peasants, instead of babysitting directionless life-hating scientists in exchange for orbs.