Game-Breaker: Arty Wario's upgrade gives him the ability to draw health refillers.
Goddamned Boss: Stuffy the 64th. Fall back a room and he refills his health. Get caught by Cannoli and you have to do the whole fight over.
That One Boss: The second form of Terrormisu. You have to use Cosmic Wario to hit a selection of three heads that pop out of holes in the wall. The catch is you have to hit all of them in one shot, which is deceptively harder than it looks. Though it is possible to cheese the fight by standing in a specific spot where the boss can't hit you.
The Woobie: The Lurchin enemies. As it says in the Monster Compendium: "This emotionally fragile urchin hurts everyone he touches, no matter how hard he tries not to. He spends each night sobbing from nearly unbearable loneliness."