Awesome Bosses / The Binding of Isaac

• Loki, an always-smiling demonic baby, is quite preferred over Monstro II as the boss of the fifth floor. They even call him "Mr. Cool" in the credits.
• Satan, boss of Sheol, is the most complex boss fight in the original game and is the only boss to have multiple complete health bars. Before he even lets you fight him, he sends out one of The Fallen at you, and once you beat him, he breaks out of the statue and goes berserk, using updated versions of The Fallen's attacks. And after you beat him... he gets right back up, flies offscreen, and uses Mom's battle strategy as the fight becomes more fast-paced with him constantly stomping on the floor. After you beat him here, he finally falls and gives you Ending 11.
• Rebirth naturally tops Satan with Mega Satan, who combines Giant Hands of Doom, mixes in minor elements of Bullet Hell, and summons at least thirteen Degraded Bosses with a grand total of eleven phases. And then he still has one more form left, where he goes all-out with the Bullet Hell in a last-ditch effort to kill you.
• Afterbirth's Ultra Greed due to having a unique gimmick involving coins that, if not destroyed, can unlock doors that summon enemies, and Hush due to being the game's biggest example of Bullet Hell but this time in a 2x2 room. Both also have damage resistance which scales depending on the damage you're doing, so even if you're on the most powerful run of your life, they still won't become an Anti-Climax Boss and die in one hit.
• In Afterbirth+, we have Delirium, the ultimate boss of the game. While he starts in his true form, he starts mimicking the other bosses in the game, including other Final Bosses, with absolutely insane attack variants.
• The final boss of the Alternate Route, Mother. The game drops all pretenses and flat-out indulges in insane Bullet Hell, with grids of bullets, lasers, shock waves, and enemy summons. And once you've depleted its health, the boss' head bursts out of its body and keeps attacking!
• As far as regular bosses go, Rotgut is pretty awesome too. It starts out normal enough, with you fighting a Sarlacc-esque monster that has admittedly tricky-to-dodge attacks, but once you deplete its health, it sucks you into it and the fight continues inside of it, in a 2D Crawl-space battle! First, you have to kill a giant maggot inside of it, and then you have to kill its testicle-like organs; killing both causes it to spit you back out, and ends the fight.
• The Visage is another well-liked battle for being a very well-executed Dual Boss. The two parts of The Visage will fight you in tandem and interact with each other in a lot of their attacks, and unlike Mask of Infamy, you have to constantly deal with both of them instead of simply defeating them one at a time and the Heart actually puts up a good fight with a number of tricky attacks across three phases.
• The boss before The Beast, Dogma, especially with the bombastic fire-and-brimstone preacher accompanying Isaac destroying what corrupted his mother.
• The Beast, the True Final Boss of the game, is an Unexpected Shmup Level that takes place in Hell itself. First, you face Ultra versions of the Horsemen of the Apocalypse. After defeating all four of them, cue the Beast itself facing Isaac in battle.