Originally Posted by Lord Natural
Gate of Madness was difficult simply because there's only so much you can do with 3 hero slots. The Torturewebs will wipe your group easily with Liquid Flame and Fireball, so you need stuff like shelter, migraine or dazed, a load of interrupts, etc. Fitting all of that into a H&H setup, plus adequate healing and damage, required more patience than I had. I just got a friend to help and we completed it easily with a full setup.
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Prophecies: Ring of Fire and Abaddon's Mouth. Ether Seals are not fun...
Factions: Vizunah, Tahnnakai, and Raisu. "let's throw lots of enemies at them" is just bad game design, period. The time limit on the latter two sure as hell doesn't help either. Imperial Sanctum and Arborstone can be hard, the former because a good portion of the celestial skills SUCK, and the latter because Danika is an idiot even by NPC standards...
Nightfall: Jennur's Horde and Dzagonur Bastion. I completed the latter only twice, and have never been able to do it again...