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Nightmare Fuel: Killer7
Killer7 has such fascinating boss encounters as a pair of Japanese businessmen who rise from the dead after having their heads blown open, and then attack by shooting their exposed brains at you. Also, the Heaven Smile's laughter.
The boss fight against Andrei Ulmeyda in the CLOUDMAN scenario is one of the most frightening boss fights in all video gamedom: after turning into a heaven smile, he slowly chases you through a maze of ambulances, all of which are horribly vivid and unnatural colors, and he is trailed by a huge string of what can only be described as bloody tentacles sprouting from his back, that drag his afro (which is, suffice to say, his weak point,) behind him. It doesn't help that he kills you in one hit, and thanks to the camera position you can't look around corners. Which means that there is a very good chance you will run straight into him. And to make the fight even worse, here's the boss theme.
The less said about Curtis Blackburn and his "hobbies", the better.
The more said, the better. Curtis Blackburn is a pedophile with a fetish for anime loli (Ayame Blackburn!) and he harvests organs for the US government from little orphan girls he molests. Even worse, he uses a giant car-wash abattoir hybrid, that rids the body of all organs, cleanses it and closes it up, then leaves just a shell of the dead body. After the boss fight in the room outside you can see naked little girl hollowed out dead bodies. In the end, in an ironic twist, Curtis is finished off by the machine, after it's done with him he is hung on a hook and his dead empty body tumbles slowly from side to side. This troper would've lost his lunch right then and there had the game not been cel-shaded.
Greg Nightmare at the end of SMILE. He's an obese dead man still hanging from the ceiling who makes horribly distorted grunts and you beat him by shooting him in his horribly swollen balls. And after that Black Heaven Smiles appear and kill your entire party except for Garcian while sinister organ music blares in the background.
Susie's stories. She's a remnant psyche who, before getting killed by the Smiths killed her own mother by jumping out of a window with her, landing in a trash compactor. Killed her boyfriend with a rifle because he broke her window accidentally with a pebble, hitting her in the face, and also admitted to castrating lots of men. This troper was guffawed by people in GameFAQs admitting they would take head from her. (she is represented as a disembodied head)
The simple fact that nothing makes sense. The player's total disorientation makes for a constant sense of unease as utterly insane and violent things keep happening around them with little to no explanation. If ever a video game has given a truly vivid look into the mind of a paranoid schizophrenic assassin, this is it.
Those random screams in Garcian's trailer. Where the hell are they coming from!?
It seems like Samantha raping Harman as usual, until Samantha dies. However, there's a Heaven Smile underneath...
In addition to that, Samantha constantly raping and abusing Harman.
The Heaven Smiles are among the most horrifying regular enemies in video games. Besides the ones Duplicator Smiles, Mother Smiles, and the Final Boss create, they are humans that are either filled with ecstasy from Kun Lan's God Hand or injected with an unknown substance. This causes them (with a few special exceptions, most notably Akiba and Kurahashi) to be in an eternal state of happiness to the point of only being able to laugh and follow a single command: "One Heaven Smile must kill one human being." Their bodies are then horribly altered; they've been given a bomb organ that they can detonate at will and naturally cloak into the scenery, with only very, very few people able to see them, and even then, most need a special ring. Oh, and they're everywhere. Once you hear their laughter in a level, they're coming for you. And pray you're in a place where you can find them...
hand in killer7 gives us the Adult Fear that is Checkbox witnessing his wife and daughter turn into Heaven Smiles right in front of him, after his entire squad was killed or turned into Smiles. He then proceeds to shoot them to death...