Awesome / Zack & Wiki: Quest for Barbaros' Treasure
Shooting the giant squid in the face with a giant crossbow attached to the ship's deck after an epic battle in the middle of a stormy sea. The whole level also sets a fine example of team work between your former enemies and yourself, as you team up with rather than use/run away from Rose's goons. The heavily pirate-themed music in the background is the seasoning, and these are all qualities to be the Best Boss Ever.
Zack headbutting Barboros in the middle of space and then subsequently itemizing him and freaking Gygaros all while succesfully fighting off a black hole.
Johnny, who has throughout the whole game hid away from danger and left all the work to you, decides not to leave you behind during the final boss, which is miles more dangerous than the game's previous events. He knows when to get serious.