These are what we call the 'YMMV items.' Things that some people find in this work. We call them 'your mileage might vary' because not everyone sees these things in the same way. This starts discussions in the trope lists, a thing we don't want. Please use the discussion page if you'd like to discuss any of these items.
Also, the constant banter between Jeremy and Hexor in the final battle.
After Jerry has his Internal Monologue at the end of the game, Jeremy breaks the dramatic mood by saying "You suck at monologues."
The Demon Cursor boss fight. Tough as it is, you're still fighting a possessed Windows mouse cursor flinging windows and assaulting you with text while epic orchestral music plays in the background. And just to make things more ridiculous, Jeremy slaps a picture of an anime girl surrounded by sheep onto the background to mess with Jerry.
Crowning Music of Awesome: The BGM for Black Rock Fortress and the overworld BGM after The Darkness takes over. Also, every single battle theme.
Special mention should go to "Earthbones", the boss music for any Climax Boss, most particularly Necrobane and the Shroud Lord.
Fridge Brilliance: After completing the four bosses of Metropolis, a gateway to fight 'Mr. X' appears. Since it was Wily's alias in Mega Man 6 games, most people wouldn't think anything of it. Who's the boss? An X clone.
Goddamned Bats: Each area has some kind of them, for example, the Hideout has Aero Scanners. Conversed with the 'Moles' (falling drills) of the Mega Man area.
The map titled "Think and act fast" in the Secured Data Segment. It takes Corridor Cubbyhole RunUp to Eleven, and if you die, you have to start the entire thing all over again. "You have to be quick" a while ago was bad enough, but this... Additionally, odds are you are short on healing items due to the plenty of tough enemies before. Have fun warping out and doing the last few already hard rooms again.
The Interface Screw room in Distortion Windows. The caption says that you're going to hate the author for it, and he's absolutely right. The screen rotates left and right as you move, easily reaching a 90-degree angle and beyond, while the game window (you get kicked back to Windowed Mode if you're on full-screen) moves left and right along with it. Add to that a switch hunt (one of which is guaranteed to end up off-screen and unseeable thanks to the screen rotation,) bottomless pits, lots and lots of enemies that can't be hurt by anything but one element, and the whole "guiding a mouse cursor to move windows to use as platforms" gimmick present throughout the level (while the cursor is rock-stupid and will almost always grab the window you don't want it too,) and it's nigh impossible to finish the room without wanting to punch the author in the face. Right after your neck stops hurting.
Note that this one can be avoided simply by placing down an Earth Shift rock and running against it. As the window tilts left and right according to your movement, even running up against a rock will cause it to change. Window getting too lopsided, just run against a rock for a bit, and you'll sort it out.
Even Better Sequel: Claire is far more mobile and maneuverable than Jerry, and the controls are greatly simplified and streamlined (while the previous game had so many buttons that you couldn't map them all to a controller, which is kind of a problem for a Nintendo Hard action-platformer.)
Continuity Lock-Out: Many plot points and references don't make much sense if the player hasn't completed the previous two games in the series.
That One Level: The Water Temple in Gate 2. It is a labyrinthine dungeon full of complex water-shifting puzzles that can take a very long time to fully wrap your head around. Reading the Dev Comment in the skull fish enemy scan reveals that this is exactly what was aimed for.