It would have to be, hands-down, the Pygmy Skulltula from Twilight Princess. There was a grand total of one in the game, and to make matters worse, the moment it saw you, it would attempt to charge at you and unfortunately land head-first into the water, where it would die a slow and painful death.
You encounter this thing in the Forest Temple. Poor guy; doesn't even have a chance to fight back. If you encounter it the "regular" way, it'll die. There's another way to the side of encountering it, though; that's the only way you can actually fight with it.