Ahh, was waiting for someone to make this thread.
I'm amazed nobody mentioned the Big Room - that's top score in my hate list.
You just can't cross it even if you're not going to pacify it without some bloody summoner appearing and summoning crap in your face.
Now, when you pacify it, you get dozens of summoners in a row, mixed with cave tigers (exactly cave tigers so you can't tame them with rat corpses), fire vortices (exactly fire ones to burn your herbs) and basically your herbs can wait a thousand turn and then grow two or three times in a row just when you're swarmed by spiders. And don't forget some giants who cannot simply walk near a locked door without smashing it.
2nd place is any level with bee hive. They're freaking annoying..