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.
Demonic Spiders: Pretty much any enemy can qualify, but particularly the explosives-using NPC's. They don't do that much damage unless on a direct hit, but they throw you around quite a lot (Possibly right into an enemy's strike) while also stunning and blinding you. Oh, and they can aim their cannons independently from their melee weapons, and it's considered dishonourable hitting them should they drop said melee weapon. Finally, most of the time they're driving the pressure-cooker airship, which unlike the others (which merely go up in flames in a mild explosion) go off spectacularly when killed, with a large enough explosion to send the large pile of weapons that's bound to be in the bottom of the arena hurtling in all directions, and to do some terrifying damage to you, depending on how close you arenote If it goes off point-blank due to the chassis hurtling around at 1 HP and smashing into you, it might just crash your game. It's that bad.
The glowing explosive bees are worse. They explode unless you hit them precisely in the head (and they generally lead with their tails). If you hit their tails (or they hit you), they explode at point-blank range, chopping off about a third of your health. They appear only once in the story, but it's very early in the game when you're just learning to fight. They return in Grim mode, but thankfully you have allies to deal with them.
Stop Helping Me!: Sometimes, your allies carry explosives (Grim missions, in particular). They do not care if you are in the blast radius before they attack. Even without explosives, they tend to leave it up to you to dodge their violently-swinging weapons.
The Escort Mission during the Silent Rock "hard" path. Bees everywhere—and that's not counting the fact that the mission has a bug that renders it Unwinnable by Mistake even before the introductory cutscene finishes, requiring endless restarting in hopes that it'll actually play!
Hammerball in the Hammerfighter's League path. The premise would be interesting were it played with teams of two actual players, or even just human AI riders—but instead, you play alone against one (later two) machines that push the ball harder than you, take no damage and do not get stunned by doing so, and are invincible—yet can and will trap and kill you even though your health regenerates during the match.
While bosses can be expected to be difficult, when the game pits you in a room with half health, myriad explosions, having you retrieve your weapon (a hammer, no less) from the ground—not exactly easy—as soon as the fight begins, and waves of two enemies at a time ... you'll wanna throw your mouse across the room. The part that makes this hard? Lots and lots of smoke to make it hard to see what's going on.
The battle inside the Pendulum right before the end of the game. Some of the toughest enemies appear, and it's very dark and hard to see. It's very easy to get murdered right before the end by a random buzzsaw out of nowhere.
Try both the Goddamn Bats (buzzsaws) and Demonic Spiders (mechanized versions of the Sakit with either guns or shocky bits, who are impossible to stun and hardly ever stop charging straight at you.)