These are what we call the 'YMMV items.' Things that some people find in this work. We call them 'your mileage might vary' because not everyone sees these things in the same way. This starts discussions in the trope lists, a thing we don't want. Please use the discussion page if you'd like to discuss any of these items.
Demonic Spiders: The friggin' orc cryomancers! Soldiers, master assassins, blood mages... are all fine, but for Starclan's sake NO CRYOMANCERS.
Master Archers (or all strong archers in general) are also notorious for dishing out tons of damage and being able to pin heroes to the ground.
Lightning Elementals are a nightmare without lightning resistance, as even the lesser versions can hit you for up to 100 damage, and the greater versions have high damage resistance. Did I mention that one early game quest has you fighting a small army of them, in an open area with little cover?
Fridge Logic: Players with high Cunning will be able to realize that the Apprentice Mage who starts the quest to be accepted in Angolwen is in fact Archmage Tarelion, one of the most powerful mages in the world. So why can't he use the Master's Staff of Absorbtion without dying?
He isn't anymore, and in any case, the Staff is an incredibly high-power piece of Sher'tul magitech, the greatest weapon of the Godslayers. The only non-Sher'tul confirmed to have ever safely used the relics of the Godslayers was Linaniil, when she drained part of the power of one of the gods they killed to become her current immortal overpowered self.
Squick: The Orc Breeding Pits, so much so that Darkgod actually had to remove it from the game once it went on Steam. (Well, that's one of the reasons. The other was that its current form was immersion/lore breaking as it could be accessed well before you stumbled upon the Orc subplot)
That One Boss: So many. Bosses are seriously nasty in the early game, but slowly become more manageable over time.
Bill the Stone Troll, secret boss of the Trollmire, although technically an Early Bird Boss, is a serious stumbling block for new players.
Wrathroot, boss of the Old Forest, has a reputation for jumping out of nowhere and oneshotting characters before they have a chance to react.
The Greater Mummy Lord, boss of the Ancient Elven Ruins, can turn invisible, hit for 300+ damage, and freeze you solid.
Your Cursed clone, who is summoned by the boss of the Shadow Crypt, has all your abilities, all your resistances and then some, double your health, and is boss rank while you're only elite rank.
The Chronolith Twins. Hundreds of powerful spells, including the ability to teleport you around the arena, they're constantly on the move, and they're incredibly hard to out maneuver. Melee classes in particular are in for pure hell. It doesn't help that the arena is 80% water, so if you don't have anything that grants you water breathing...
Demonic Spiders: The Floating Eye, an early game monster that can instantly kill you if you move into its melee range, due to the tendency for most players to play with Berseker / Running on, making them extremely vulnerable to it's attacks. Worse still, they have a tendency to spawn RIGHT outside of viewing range, meaning you'll turn a corner or use the automated run-down-hallway buttons and end up right in front of their face.
Game Breaker: Lots in the 2.X series, considering the sheer number of class / race / subrace combos. Some particular standouts:
Summoning — a skill that allows you to create monsters based on bits of their corpses. Where it becomes broken is that Summoned monsters can summon monsters or breed into new monsters. Which means a summoner can summon 1 or 2 White Rats, or perhaps 1 or 2 Great Wyrms of Power, and let the resulting army clean out the map.
Necromancers — Doesn't seem overpowered, until you realize that hacking a monster into 50 pieces counts as 50 different monsters for the Raise Dead skill.
Possession — a skill that allows you to switch bodies with a dead monster. All the exploits of summoning, only now you control when they get used, not the AI. In addition, there are certain bodies such as The Watcher In The Water, which give you the ability to wield an absurd number of weapons at the same time, or a Great Wyrm of Power, which are normally That One Mook, but now under YOUR control.
Alchemy — While Alchemists are extremely weak early on, they get the ability to turn gear into items that are beyond anything else in the game, with a LOT of work. Ultra high end Alchemists can literally make themselves immune to all damage, able to move faster than the gods, attack dozens of times a round, etc etc.
Goddamned Bats: Literally. Fruit Bats move just fast enough that a melee character can't catch them, and do nothing other than interrupt your resting and movement. Later variants are just as annoying, with the added bonus that if they see you with low HP, they'll dive in for the kill — and suddenly the absurd movement speed is a lot less annoying and a lot more scary.