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.
The Horned Girl's lack of thoughts or personality, Longneck's creepy masochist attitude, and the fact that you're the only one who looks and acts like an actual human being in the game.
The boxbearer's breakdown, he and the revelation that he killed his own daughter (The Bagged One) in a fit of madness. He become so distraught he deluded himself into thinking his empty box contained his daughter's soul!
Once you actually see what the Meta-beings look like, it will frighten you to think they were once human! Even worse is when you read the Meta-beings' baroques, which are stories of how they became the way they were
The moment that you realize that the Horned Girl isn't speaking what she's thinking, but rather what you're thinking.
Being a confined, dungeon-like space with all these Metabeings, and not knowing what's in store when you advance to the next level... *shudder*
Advanced Angel. . . looks dead when you find him in the original. YYMV if it's better or worse that he is both awake and alive in the remake.
That One Boss: The only four bosses aren't even required to beat the game, technically. And boy are they HARD. Even worse, after you beat them in the Neuro Tower, they become normal enemies in the Coffin Guy's bonus dungeons.
Uncanny Valley: Most of the creatures in the game fall under this, to some. The remake making everything slightly more cartoonish may make it even farther.
Its kinda strange how some characters like the Protagonist, Archangel and the Absolute God are drawn in typical anime style yet others like the Coffin man are drawn in a more realistic manner.