Titan Quest/YMMV

Anticlimax Boss: You're lead to believe that you'll have to fight Minos and the other judges in the aptly named Tower of Judgement, but instead you're attacked by a crazed Cerberus and then Minos will simply let you pass without a fight.
Demonic Spiders -- The game has mutiple examples.
- Also the Dragonians in China are awfully though: they always come in large groups, are really strong and resilient and can torch you into oblivion with their Breath Weapon. And don't let me start about their Undead counterpart in Mount Wusao's Cavern.
- Some of the bottom tier mobs have disproportionately high attack power. A point blank Ao E character (e.g. a Defense Mastery specialist) can be torn to pieces if surrounded unless heavily optimized. To be safe, test the trash in each new area before going in.
Goddamned Bats -- Many enemies will flee when injured, particularly the weaker ones and those with ranged attacks, necessitating a chase (or re-click if the player is also using ranged attacks) to finish them off.
- There are also bats, but they don't fall under this trope.
Scrappy Mechanic -- Dying always close your town portal, forcing you to backtrack all the way from your last rebirth fountain to the site of your death. This can very frustrating, since the last rebirth fountain can be very far (the Manticore's lair is one of the most notable one). Worse, monsters can kill your near your rebirth fountain, turning your entire existence in an endless cycle of life and death in a mere seconds.
- Cooldown. Some of them are painfully slow to recharge your skills, with the longest being 6 minutes (Summon Outsider and Colossus Form). Using scrolls also has a cooldown, even when you try to use a different scroll. Even drinking potions has a cooldown for crying out loud!
That One Attack -- If you let Typhon hit the Hades Statue on Olympus, he'll briefly gain an extremely powerful vitality-draining attack that will murder you and heal him to the max. Even if you have 100% protection from vitality attacks.
That One Boss -- An extremely powerful, large skeleton called Toxeus the Murderer who can appear randomly in dungeons, capable of killing even the most powerful characters in one hit if they aren't very careful. Simply running past him and moving on is usually the best option.
- There's one place where Toxeus will always appear, the Secret Passage, accessible near the start of the fourth Act if you have an item called the Overlord that the final boss sometimes drops. He doesn't need to be killed to loot the massive chest at the end of it, but it's hard if you don't have the appropiate skills. Still easier than killing him, though.
  - Also the first Telkine Megalesios is quite a pain in the ass, if you don't kill in time the two life-sucking demons he summons in order to prevent him from healing himself
- The Cyclops is pretty much a crash course in the art of hit and run combat. He has a mountain of health, hits ridiculously hard, and one of his special attacks is a roar that instantly halves your current health. You pretty much need to use stunning abilities or, failing that, hit him a few times and run before his roar triggers. Oh, and he comes out of nowhere with no buildup, so you won't know he's coming until he's literally beating your face in.
- Alastor, Scourge of Acheron has a massive life leech, has a ton of health for his level, and can summon up to a dozen high-powered skeletons. Yeah, not fun. Unless you play as a Theurgist and max up the harming-undead thing.
That One Sidequest -- Most sidequests in the game are somewhat short and to the point. However, one sidequest in the expansion Immortal Throne requires the player to find four gems, used to unlock the gate to a room full of goodies, free to be looted. The gems are rather easy to find, however they're very far apart (one is found right before the final boss, while the sidequest is taken with about 3/4 of the expansion's campaign still left), which may severely confuse players who're doing it for the first time.