Mountain Pass, the vehicle level from hell. It has one-hit-kill exploding barrels, dodgy environmental collision detection and obstacles that are impossible to avoid without slowing down or playing the level again twice, all on a bike-type vehicle that already has a wide turning axis. Oh, and to cap it all off, IT'S A RACE!!
Spider Cave. It's friggin' HUGE, and extremely confusing to navigate. There are massive pits of Dark Eco everywhere, so your jumping skills need to be dead on and you have to be very, very careful. This wouldn't be so much of a problem if its Power Cells weren't some of the most gruelling, tedious and difficult to get in the game, and it's filled with tough enemies. It doesn't help that a lot of it is a borderline Blackout Basement either.
Most of the game could count, considering how hard it is, but a major offender is the Hellcat mission. And the Escape from the Water Slums. Hint: it's possible to punch your way out; simply keep hitting the square button. JET-boarding your way to safety also works if you know the route well enough.
DAMN YOU INVISIBLE METALHEADS! Also, the march to the Metal Head leader which is topped off by the boss himself.
The mission where you have to destroy the walking bombs that are headed for Torn's hideout. Each one takes a TON of firepower to destroy and peppers you with bullets if you get so much as an inch too close. (Crashing a motorcycle into one first helps.) Additionally, you have to navigate your way through the city in the most timely manner possible in order to meet the strict time limit. And, of course, this is an illegal mission: hello Krimzon Guard!
The Drill Platform mission is notoriously Nintendo Hard on Hero Mode. Now that everything is twice as hard to kill and none of your Hero Mode stat bonuses are any use, the mission is a true destroyer of hope.
The carry the eco transport mission near the beginning of the game is a pain as well. Among the few known methods to complete it are flying over the water while being chased, with an extremely weak scooter as your mandatory transport.
The boost ring race against Erol is particularly rage inducing. The course is long and difficult, pedestrians get in your way and slow you down when hit with alarming regularity, and your opponent will do everything in his power to push you off course, since missing a single ring causes you to fail the mission. Even worse, Erol has no such restriction; in fact there is one ring in particular that he almost never actually bothers to hit. Rubber Band A.I. is in full effect. As an added "screw you" to the player, winning the race opens up some new side missions for precursor orbs — one of which is, you guessed it, doing the whole race over again!
The mission where you escort Krew's men into the sewers. You're forced to protect three A.I.s who offer little to no help during the mission from Metal Heads. The Metal Heads in particular that you fight have the ability to shoot lasers, so God help you if they get the jump on you when they're offscreen. The true kicker is the last leg, which has an auto-save that doesn't trigger, involves a giant swarm of these metal heads attacking you all at once. If any of the A.I.s die, you have to restart the mission from the beginning.
Missiles follow the vehicle you're on all the way to the docks area. You have to go around the docks, shooting buoys to make them light up so the missiles will go for them instead of you. The missiles are fewer than five feet behind you at all times; only one (out of around seven) will attack the buoys at a time; you have to fly low enough that the missiles will lock on to the buoys, but rapid changes in altitude will usually cause the missiles to catch up; you can't just stay as low as possible because of the low bridges in the area; the missiles don't always lock on to the buoys; you can't turn too sharply or for too long; you can't go straight for too long; and even if you're doing it perfectly, they'll catch up anyway.
This in no way forgives the mission, but you are rewarded by seeing the Naughty Ottsel's mascot get his head blown off when you get rid of the last missile. It's a much better reward than the one you get from the Slam Dozer mission with Damas, which may be the biggest Tear Jerker in the game, followed by another vehicle-based mission that may lead one to throw his or her controller at a wall.
Hello level "stick Daxter on a rocket at a gazillion miles an hour and make him try to get through accelerator rings that have handily been placed all around the harbour, whilst avoiding pedestrians and guards and constantly accelerating". The result of your constant crashing is a surprisingly chirpy Daxter making a sarcastic comment about your skill.
There is an unfair race near the beginning of the game, where you have to race a group of monks on a leaper lizard. The problem is that hitting a pedestrian will slow your leaper down, thus forcing you to constantly restart to get an optimal randomly-generated crowd. On top of that, the monks can damage you with their leapers (which of course you can't do), causing you to come to a full stop. Fun!
The mission "Defend Spargus from attack", where enormous Metalheads are approaching the beachfront and you're the only one in their way. There are way too many targets you have to hit on them for just one of the deathbots-from-hell to blow up; your turret catches fire; and if any of the Metalheads make it, you immediately die.
From Daxter, the Lumber Mill. It's huge and confusing, full of enemies, and has irritating obstacles. Especially the part where you have to fly above a lake, where the fish jump out and kill you if you barely fly over it, while you're dealing with spinning platforms and temporary platforms, and with not enough eco pickups. Your main objective forces you to wait for eternity on a switch while the bug zapper charges up, while the giant bug drops "bombs" at you. It's one of those stages that takes forever.