Fire Elementals, and to a lesser extent their smaller cousins. They're insanely tough (because they're made of fire), damage both your armor and weapons (again, fire), and have a nasty habit of appearing in packs. One quest actually forces you to trek through a cave full of these things.
Golems are this to a lesser extent, especially since you're forced to fight them a lot earlier than you'd normally be ready unless you abuse the mechanics to jump ahead 30 levels. Like Fire Elementals, attacking them damages your weapons since they're made of rock. Some of them also come superheated for fire damage, making them almost as bad as Fire Elementals.
Finally, at the bottom of the barrel but still no less annoying, are the blue zombies. Not only are they at least twice as tough as any other zombie, they cause fire damage when they strike. Sensing a pattern here?
In an example that surprisingly doesn't involve fire, the barbarians at Kree are some of the toughest human enemies in the game, easily equal to a late-game melee character. To make it worse, it's extremely difficult to attack them without getting mobbed by several at once. A resurrect spell or tech-based alternative is highly recommended, and they are prime zombification targets for the same reason.
Disk One Nuke: Should you choose the magical path, Harm is the first level Dark Necromancy spell. It costs a pittance of Fatigue, deals decent damage for its cost, and as befitting of spells, doesn't miss. Its only disadvantages are that it dings your Karma Meter every time you use it (you'll quickly offend your good-aligned party members) and it won't be as useful lategame (what do you expect of a first-level spell? By this point though, you most likely would have far better options as well).
Enjoy the Story, Skip the Game: It's often considered as having an excellent story, dialogue choices and level-up options but with mediocre combat gameplay. The combat can get in the way of the story, as there are a plenty of unskippable fights, some of which can be quite hard, especially at the beginning when the player character can die in a few unlucky hits.
The Explosives line for technologists becomes absurdly powerful if you invest in it and throwing. Almost all of the crafting recipes have materials which can be scoured from trash bins, they can be sold for massive profit, and the higher level schematics create deadly combinations. You'll have a character who can stun an entire room and then blow them all up before they know what hit them.
For melee technologists, Smithy is just as broken. Balanced swords can be created in the first town or have Magnus make them for you by the second. They have one of the the fastest attack rates in the game, but still have good damage. The next step up is the featherweight axe, which is slower but stronger. The axe can then be upgraded into the deadly pyrotechic axe, which pound for pound is pretty much the deadliest tech melee weapon in the game thanks to fire being such a broken damage aspect. The only things that outclass it are Infinity+1 Sword weapons. After that, you get to make the best tech armor in the game.
A minor one for technologists is the electric ring in the second level of the electric tech tree. It gives a +2 to Dexterity when worn. You can wear two. In a game with only 60ish character points to give your character, four extra is a huge bonus, minus the two you spend to get there. If you're going for electric mastery, then it might as well be four more points.
Similarly, if you go the magic route and specialize in Force magic, you will eventually be able to cast the Disintegrate spell at half endurance cost. It will completely and instantly vaporize whatever it hits, essentially letting you run all over the place destroying anything that stands in your way, be it monster, NPC, or a door. It destroys loot, which is something of a downside, but there are a lot of things to kill that do not drop loot (or drop worthless loot).
The fifth-level time magic spell tempus fugit speeds your party by a factor of two, and slows everything not in your party by the same factor (no saving throw, no immunity, magic resistance does not apply). It has a large up-front cost, but the cost to sustain it is trivial. It's every bit as broken as you would expect for something that increases the number of actions your party gets per enemy action by a factor of 4.
Fatigue slowers halve the fatigue cost of all spells while they're active. Combine that with fatigue-restoring potions, and you can throw around several hundred fatigue points worth of spells without rest. And yes, that can be combined with Force mastery, which allows you to Disintegrate the entire population of The Very Definitely Final Dungeon.
The dog. Really high damage, fast attacks, and usually hits. For added cheapness, he even automatically gets the mastery bonuses that you have to either pay or work your ass off for. Makes combat a bit too easy, and kill-steals like you wouldn't believe.
He can even bite open doors and chests inflicting only minor damage to himself. You do not need keys or unlocking skills/magic anymore.
Every combat skill has a matching uber-weapon, almost all of which become available at an appropriate stage of the game. However, Throwing specialists can obtain the Aerial Decapitator around halfway. Finding it may be a Guide Dang It, but after that you have a one-hit killer that requires no ammo and doesn't break. It's also one of the fastest weapons, so even if the first hit isn't lethal, your opponent probably won't be able to retaliate before the next one does the job.
Even though it's somewhat late-game, the healing mechanical spider gifted to the PC by returning the camera from the crash site counts. As soon as you have it, forget any possible need for any type of healing. One spider, so long as you can keep your party alive, will heal anything short of a maxed-out mage.
And the late-game aspect is dropped if you can navigate to a certain mountain passagee and cross it in reverse direction.
With just a few points invested in Pickpocket (or Save Scumming), you can steal a key from Ristezze, a merchant in the first town, allowing you to open his loot chest and take his entire inventory (It's mostly junk, but technologists can craft some of it into useful items) and all of his money (usually about 1300 coins), and continue to do so every time you visit Shrouded Hills for the rest of the game. Never again will you worry about money.
Once you find the Necromizer schematics, you can turn some of the most dangerous enemies in the game into your eternal zombie companions. And if they die, just revive them again. The ingredients can be bought or stolen from shops, so you craft an endless amount, for free if you have the lockpicking skills to rob them.
As soon as you visit Tarant or Blackroot, you can take a train to Ashbury and then dart straight to Vendigroth ruins. With some speed potions you can run past most enemies and get yourself the components and schematic for what may be the best firearm in the game, but if you are willing to pack a couple of invisibility scrolls and explore further, you may also get a chemical that raises all your stats by 1 permanently, and an army of battle robots.
Genius Bonus: You shouldn't be surprised that the Zephyr is doomed once you see its interior: the staircase and lounge look just like those on board the Titanic.
Good Bad Bugs: The Reflective Shield spell has a certain unorthodox application. Normally it reflects any spell cast at the character with the shield on them back at the caster, this goes for both beneficial and damaging spells. However, the shield treats canceling sustained spells as a spell in and of itself. Meaning if you cast, for instance, Polymorph on someone, then cast Reflective Shield on them and then cancel the Polymorph, then the cancellation will be reflected back at you, the Polymorph effect will be removed from your sustained effects bar but will not be removed from the target, meaning they are now permanently a sheep. This works for any spell that needs to be sustained, including Mind Control and summoning creatures.
Hilarious in Hindsight: Gilbert Bates, the presumed inventor of the steam engine, who holds the monopoly on making steam engines, is a reference to Bill Gates of Microsoft. His competitor, Cedric Appleby (probably an Expy of Steve Jobs), is a reference to the Apple corporation, who competes with Microsoft. Today, Apple has already surpassed Microsoft as the bigger tech company made famous by their I-Products such as the iPod, iPhone, and iPad.
With a market value of about $460 billion, Apple is worth more than Google, Goldman Sachs, General Motors, Ford, Starbucks and Boeing combined. – Apple is now worth almost twice as much as Microsoft (about $258 billion) and more than twice as much as Google ($198 billion).
Moral Event Horizon: Garrick Stout became captain of the guard purely so he could stalk a noblewoman, and when he found out she was already engaged, he rendered the fiancee blind in what was promised to be a fair duel, then arranged for the fiancee to become trapped in a cave full of monsters solely so he could save her (or have the player save her on his behalf).
Charles Bregho and his friend Farcus murdered the wife and daughter of elven priest Arbalah after guesting with him, and stole his sacred artefact.
Murdering the population of Stillwater is one for you, if you join Dark Elves.
Gnomes of Tarantian Industrial Council crossed this with their vile experiments on breeding half-ogres, using human women and queen of Tarant as breeders, murdering the king and his family with many nobles, after king's clerks uncovered their plan.
Auto-scheme (allowing the game to automatically spend skill points at level-up). While it grants some gameplay challenge, it wastes many skill-points on Dump Stats like Health and Fatigue boosts. Pre-made characters use this by default, but fortunately, you can turn this off anytime.
The way your followers may negatively react to whom you choose to attack. While it's not a bad idea in principle, this mechanic has a very nasty habit of firing off in the most bizarre of situations, like when you choose to attack an already hostile creature before they had a chance to see you.
That One Attack: As noted in Demonic Spiders above, anything with the potential for fire damage is immediately at least twice as dangerous as any other form of enemy. Fire damages equipment, most things are not resistant to it, and the enemies that tend to use it are also usually much tougher than other enemies. Fortunately, if you get your hands on something with fire damage, like the pyrotechnic axe, it's just as broken in your hands.
The Black Mountain Clan Mines. It's the only part of the game you can't talk your way around. Moreover, it's filled with rock golems which break most weapons when you attack them and do insane damage compared to what you've been fighting thus far. While there are other difficult combat-heavy areas, The Black Mountain Clan Mines are more notorious because they are a relatively early part of the main quest and because you can't get around doing them.
To a smaller extent, getting out of the first town can be this for the violence-inclined and/or those without the right build. In order to leave, you have to get past the guys guarding the bridge. Unfortunately, the leader has two half-ogres who will beat your party to death in short order. You get stun grenades early on, but without throwing skill you have to save scum for a solid hit. To get past charitably, you either need a ton of money (more than you're likely to have or want to spend), to sabotage the new bridge being built (which will make the town hate you), or a single skill point in persuasion. You can also abuse the game mechanics by dropping some railroad spikes next to the thugs. Because they're all using their fists (which do a crapload of damage), the game considers them to be unarmed. That means they will automatically pick up and equip any weapon on the ground nearby, even if that weapon does far less damage than they'd normally do unarmed. Railroad spikes have a maximum damage of 1. Your team should be able to beat them now. The point is still good, though: without knowing how to take advantage of the game mechanics like that, that's an early-level Beef Gate that has put a fair number of people off from playing the game any further.
T'sen Ang if you choose to free the half-ogre slaves. Everybody will turn hostile and they can be quite difficult.
At least Kree is optional, but the barbarians there are very fast, hit hard and are often in groups. You'd better bring along a necromizer or two.
They Wasted a Perfectly Good Character: Jayna Stiles, whose status as the sole tech-based healer makes her a very useful follower for tech-based PCs. Despite a sympathetic backstory that ties into the general state of affairs in Dernholm and Cumbria, she has no bearing on the actual quests centered on that kingdom, or the main plot. And to top it off, she doesn't even have voice acting.
Unwinnable by Insanity: The developers went out of their way to avert this; at worst, you should be able to find the next main quest by consulting a guide and walking around randomly in the right place until you find a relevant location. However, if you kill Edward Teach before going to the Isle of Despair, there isn't a workaround for that. Other than that, as a developer interview indicated, if you go out of the way to break the game, all you're doing is making it harder on yourself once you stop screwing around.
The Woobie: Randver Thunder Stone loses his father to exile long before he's ready to inherit the throne, and he gets no endings that aren't at least somewhat bittersweet: either his father returns to the throne and he isn't even mentioned in the ending, his father dies heroically and allows him to become a good ruler, or his failures as a king lead to a civil war that either causes him to lose the throne to a stronger candidate, or drives the dwarven race to near-extinction.
Woobie, Destroyer of Worlds: Poor Torian Kel. After his resurrection he's on a hopeless quest trying to find a way to release his trapped friends. But what makes him a Destroyer of Worlds? Besides being evil aligned, he's willing to side with Kerghan's quest in exterminating all life so said friends can be released, making him a literal example of this trope.