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: Kobold Shamans on elite mode know lightning bolt spells. And use them a lot. Failing a reflex save means bye-bye to half of your health if you're a fighter, or all of your health if you're a wizard. At higher levels, you meet beholders, one of the game's nastiest monsters who tend to repeatedly use a Disintegrate spell from their Eye Beams, which is likely to kill you in one shot as well as damage or destroy all of your costly equipment.
Goddamn Bats: The actual bats are hard to hit if you aren't using auto-target, and auto-target is slower than the manual mode. Go figure. There's also rust monsters that pretty much have to be dealt with via ranged weapons, a wooden club, or magic (they eat metal), oozes that similarly eat whatever hits it other than ranged weapons and are best handled with Good Old Fisticuffs or a rare crystal Muckbane club, spellcasting enemies that know Hold Person/Hypnotize/Daze Monster, trolls that have to be finished off with fire or acid (unless you have epic damage output), the large spider enemies that keep jumping around when they attack, etc. etc.
Heartwarming Moments: Gary Gygax, co-creator of the original Dungeons & Dragons game, actually narrated one quest arc, Delara's Tomb. After Gygax's death in 2008, the developers of DDO created an in-game memorial in Delara's graveyard (which includes a d20 dice on the stone memorial). A similar memorial appears in the Threnal quest chain for D&D co-creator Dave Arneson, who narrated that quest series.
Gnarkill, Troll Butcher in the Waterworks area is the first troll parties are likely to encounter. His regeneration combined with heavy damage-dealing capabilities make him difficult for parties that do not know to use fire or acid. Considering that flaming and acid weapons are not common at low levels (Perceptive people might notice the very helpful flame trap with a pressure pad on the right side of the room)...
First General Horoth in the Tower of Despair raid has around 2 million health, hits hard, and regains 20% of his health if a party member dies. He also has a move that will literally BANISH those not wearing Boots of Anchoring,them back to Stormreach, denying them completion of the raid and the resulting quest loot and will stun those who are for a short time.
Also in the Tower of Despair, the Shadowmaster is not a very strong foe by himself, but has minions that attack during the fight and deal around 300 cold damage just by being near you. If they are not kited properly, they will quickly wipe the raid.
The Black Abbot, raid boss of the Ascension Chamber, is a powerful spellcaster with 400-damage disintegrates, a move that sets the arena on fire and drains the casters' mana, a move that traps one person, deals damage, and drains their mana, and can summon invisible enemies that, you guessed it, drain mana. In addition, the battle takes place on a platform floating on a lake of death. Oh, and you need to complete puzzles to finish him off.
The Lord of Blades. He is a handful on the lowest available difficulty setting and harder than hard on Epic. On Normal, he has ~200k hitpoints (about as much as several raid bosses have on Epic), 80% fortification with a such a massive fortitude save that he is pretty much sunder proof, has several devastating AOE attacks which are capable of instantly killing almost any character if you do not evade them (requiring twitch skills), and the fight goes in several phases which involve periodically clearing minibosses while still enduring LOB's powerful attacks.
On Normal, his Challenge Rating is the highest in the game at 32. This means he is seven levels higher than the current level cap (twelve higher than the previous one). On Epic, his CR is 46.
"Proof is in the Poison" is very much a nightmare for any low-level party that does not know what they're doing, mainly due to the many casters in the dungeon that like to throw nasty spells on you. The Quickfoot Caster ambush on the bridge at the beginning has led to many a Total Party Kill.
Also, there are 3 rooms almost completely filled with acid, and you either need to navigate across pipes on the ceiling or jump on small platforms to the other side to pull a lever, causing walls to go up IN THE POOL, making it so you need to return a certain way.. Also, there's a room with acid in front of the staircases, as well as an earlier room where you will likely need to walk across a pool of acid, so your hireling will probably walk into the acid, killing him/herself.
"Kobold Assault" gets this for being the first Challenge Dungeon most players meet, It's a massive Zerg Rush of Kobolds, including their spellcasters. You have one rest shrine. It is also out in the open, this tends to involve players getting hopelessly overwhelmed even on casual.