Tyrant has the Epic Siege on Kor raid. The commander summons a Rat Catcher every turn, which can immobilize you and Phase you as well, blocking that unit from being affected by your own friendly activation skills. The core structure cards are some of the deadliest in the entire game, including the Cannon Wall, which has 15 health, and in 3 turns it Enfeebles all of your units, making them take 2 additional damage from all attacks and then proceeds to Strike all of them for 3 damage (after the effects of Enfeeble). There's also the Cluster Mine, which has Counter 10, which will pretty much kill any of your units that hit it. You think you can just Siege away those structures? Well, it also has two of its own version of the Gatling Tower, which will Strike one of your own units for 4 damage, inflict Chaos on all of your units, turning all of your own attack skills against yourself and thus blocking any Siege strategy you might employ, and Sieging all of your structures for 2 points of damage, all after only 2 turns. If that's not enough, the randomly generated player-available cards can make it even worse, including the Metalworks, the Usial, and Orwold's Reckoning, all of which can summon even more enemy units in addition to the commander's Rat Catchers. The best possible deck for this raid has only a 77% win rate, while all other raids have at least one deck with a 95%+ win rate, and it has 1.2 million health which requires great contribution from all 40 possible people to take it down within the 3-day time limit.
The Curse of Naxxramas Paladin class challenge. Class challenges are rematches against specific bosses where the player is given a pre-built deck to fight them with, usually to promote fun strategies for casual play. There were two problems with the Paladin challenge, however. The first is that the deck you were given was absolutely atrocious, relying on giving huge buffs to the Echoing Ooze card, despite the fact that the deck had very few buffs in the first place. The other problem was the fact that the boss in question was Kel'Thuzad, the Final Boss of the adventure and its greatest challenge outside of Heroic mode. Kel'Thuzad boasts very powerful minions, has access to the Twisting Nether spell to nuke the board whenever he pleases, and has a starting hero power that puts the player on a very short clock to kill him. The fight was universally detested right from launch, and was so psychotically hard that not even top Legend ranked players could beat it in one go. The deck used to fight Kel'Thuzad was later reworked to make the fight substantially easier, but even to this day the initial incarnation of the fight is considered one of the hardest bosses in the game, more than even some Heroic battles.
Chromaggus from Blackrock Mountain. At the end of his turn, Chromaggus will put a Brood Affliction card into the player's hand, which give Chromaggus bonuses while they're in hand, varying from healing him to reducing the costs of his cards. Players can cast the Afflictions for a small mana cost to get them out of their hand, but Chromaggus will also play Chromatic Dragonkins, 2 mana 2/3 minions that gain +2/+2 whenever the player casts a spell - which, incidentally, includes the Afflictions. Finally, in the lategame, if the initial onslaught is survived, Chromaggus will be able to drop Nozdormu. Normally, Nozdormu is a joke card who reduces the turn timer for both players to 15 seconds. When used by an adventure AI, however, Nozdormu will glitch out and straight up skip the player's turn. Permanently.
The Crone from the One Night in Karazhan adventure. Her fight's gimmick gives out some good news and bad news: the good news is that Dorothee can give your minions Taunt or Charge depending on where you place them; the bad news is that this is an Escort Mission with Dorothee at only 10 hit points as your escortee; if she dies, the Crone's Hero Power kicks in and gives you what's essentially a One-Hit Kill to your hero. Unfortunately, she has plenty of resources to whittle down Dorothee and your Taunt minions from Stealth minions, her exclusive Flying Monkeys with Charge and attack power that can easily land a killing blow to Dorothee, the dreaded Knife Juggler, and even Twisting Nether that destroys all minions (including Dorothee) on the field. Lord help you if you're playing on Heroic Mode, as on turn eight the Crone automatically draws Twisting Nether; have fun trying to deal 60 damage to her in eight turns.