I remember reading once that Super Metroid speedrunners call a certain room 'The Worst Room In The Game' semi-officially. It's the room in Lower Norfair where you first encounter Gold Pirates, and have to climb up a vertical room full of them while also breaking through blocks above you, then clearing them before they recover. A lot of the time they do this without the Screw Attack because it's faster without it, but without it you can't kill the Gold Pirates or break the blocks while still ascending, so it takes a lot of "extra" work to complete and tends to kill runs, especially for beginners.
I think about that every time I play Resident Evil 4 and get up to 4-2, which contains RE4's The Worst Room In The Game in the form of the Novistador hive. Novistadors are already a pain in the ass to fight, since they tend to hang out above Leon's eye level, so you need to take time to aim up at them before you can shoot them, time that they'll use to instantly close the distance on you. The sewers were mostly full of tight corridors so they have less scope to flank you, at least, and the ballroom is pretty short so it's not that bad to just run past them all, but the hive is a huge open space where they can come at you from anywhere in massive numbers, and also requires you to force yourself through narrow corridors into wide open side rooms where they can still flank you as they swarm inside, but you can't run past them. And there are no checkpoints in this room until you get to the exit tunnel with the smashing pillars, so if you die (and you will) you have to do it again from the beginning.
The one time I played on Professional difficulty, I died more times in that room than anywhere else in the game, and I didn't feel any closer to figuring it out each time, nor was I having any amount of fun with the struggle. I'm only playing on Normal this time, but I just beat up the Detachable Right Hand and now I'm dreading having to go back through there. At least it's the last time in the entire game I have to deal with the miserable insects.