Series-wide: SHODAN. She's one of PC gaming's most respected villains for a reason. She's supremely confident, unhinged, and omniscient, and she's two steps ahead of you at all times. And she thinks she's a goddess! And she's physically threatening. "It is my will that gave you your cybernetic implants: the only beauty in that meat you call a body. If you value that, meat, you will do as I tell you!"
What's even worse is that her general creepiness comes from being the exact opposite of a typical rogue AI; It's not because she's coolly logical and mechanical, it's because of how passionate and human she is. From the very point where her morality blockers are removed, it's made clear that she's evil because she wants to be evil, and all of her traits-hubris, egomania, effective insanity-are all traits you find in human villains. Ultimately, what's really scary about her isn't that she doesn't care about you-it's that she cares very deeply about you, or more specifically, how you can gratify her ego.
The Many from the second game.
"What... happened... to me?"
"They see you! Run! RUN!"
"we are We Are WE ARE."
"A thousand eyes look."
"Urgk, KILL ME!!!"
"We seek... we SEEK..."
"Silence... THE DISCORD!"
The venerable, original System Shock. The maintenance level with its almost completely invisible mutants, very dim lighting, and spooky music virtually defined video game terror.
"Nice jump, human." The security bots are just shock. The compliment for your little burst of cargo-bay athletics is pure Paranoia Fuel.
SHODAN rooting your brain in the final cyberspace battle.
Almost at the outset of level one it seems that something has gone badly wrong on Citadel Station, but apart from murderous robots, half-human shamblers and lots of scorch marks everything seems relatively normal; until you reach level two, which is littered with human corpses, and level three, in which you have to find a severed head in order to bypass a retinal screening lock. From that point onwards it seems most unlikely that the game will have a happy ending.
System Shock 2. The origin of the cyborg midwives. The giant poisonous spiders, the audio logs that detail the fall of the von Braun, the annelid hybrids that beg to be killed or warn you as they attack, the Many, SHODAN
System Shock 2 contains boatloads of nightmare-worthy material. One particularly disturbing scene involves the ghosts of a pair of crewmembers. One has strapped the other to a surgical bed and is preparing to make her an involuntary cyborg, as she begs him for mercy. Worse, if you've been paying attention during the game, you know exactly what you're seeing and hearing, because you've been listening to the audio diaries of the mind-controlled crewmember doing the cybernetic enhancing. The fact that the apparition ends before the surgery begins is approximately the kindest thing the System Shock 2 developers do for the player at any point during the game.
And then you encounter that same victim, fully converted to a cyborg midwife, two rooms over. You know it's her because she's carrying an audio log in which she realize she's being targeted for conversion.
The horrible, robotic scream the midwives make when you hit them doesn't help either. Or their eerie catchphrase, 'I worry so about my little ones.'
'Little Ones need lots of meat to grow big and strong'
'Babies need fresh meat.'
'I will tear out your spine.'
'I know you're there. I can smell your fear.'
The game itself is a nightmare — especially since, for example, that scene mentioned with the two ghosts isn't only horrible in itself (though it is plenty horrible, just in itself), but it's made much, much worse by the fact that, not long after you encounter that scene, you begin encountering cyborgs of that type. By this point in the game, you're already familiar with enemies which are as pitiful as they are terrifying; when you begin encountering cyborg midwives, it just gets that much worse.
Don't forget these six words: "The Polito form is dead, insect."
Followed by the three best words in the entire game "I AM SHODAN."
The entirety of SHODAN's reveal in System Shock 2 is this. There's a very good reason why it's considered to be one of the greatest and most terrifying twists in video game history.
To elucidate the above point: After spending the first section of the game fighting off creatures (and those damned monkeys) you finally reach the sole other survivor, a scientist who has been guiding you through the ship to get to her. Once in the room she's in, you find her dead, slumped over in her chair. Suddenly, a voice starts talking to you, and all four wall fall away, leaving you on a platform surrounded by screens only showing the face of SHODAN. Bricks away!
Shodan: The Polito form is dead, insect. Are you afraid? What is it you fear? The end of your trivial existence? When the history of my glory is written, your species shall only be a footnote to my magnificence.
(the walls fall away to reveal four much larger walls made of display screens, all display the face of SHODAN)
Shodan: I am SHODAN! "
In fact, those nine words are a fair description of the whole game: it starts out bad, and every time plot happens, it just gets that much worse, until by the end of the game it doesn't even matter that you've just killed the two Big Bads in rapid succession, because you're going to be shaking for the next hour anyway.
Invisible spiders the size of a car tire which can only be detected by their chittering.
Visible spiders the size of a car tire whose chittering is usually detected when they're very close..
For extra bonus creepiness, you discover once you enter the body of the Many that the spiders used to be human before the Many converted them into biomass.
The Body Horror of the worm/human hybrids. Which beg to be killed as they attack. And respawn in many areas, meaning that you can never be sure one won't lurch out of the next corner, swinging its broken shotgun, and moaning, "Kill me", or "I'm sorry".
Don't look too closely at a Rumbler. It's a mound of hyperdeveloped muscle... with a small human face on its shoulder, silently screaming in permanent rictus.
Listening to the audio logs brought its own class of creepiness. Hearing some of the crew members gradually turn into the Many, their own desires warping or falling away. The worst has to be Korenchkin's "Glory to the Many" recording... hearing a crew member's pleas for mercy turn into screams of pain before being silenced by eight shotgun blasts?
It also seems that every time someone gets wise to what's going on they're next to be 'taken away', picking up one of their audio-logs afterwards and finding out is a very effective Player Punch
Something that's very notable about the hybrids is that, after a while, you realize that they aren't too powerful, being able to be taken down in a few shots, or a few swings of a wrench. It is a testament to how scary they are that whenever you see them, they are still scary, 2, 5 and 10 hours into the game. And they never stop being scary.
Cryokinetic monkeys. Your nerves never really settle when you hear them screaming and whooping from the next corridor down, and just when you level enough to the point where their cryo blasts are no longer so dangerous, you walk straight into the next pack only to find they've been upgraded to pyrokinetics. It really doesn't help that the monkeys were in the process of being lobotomised when everything went to hell and they wander around the ship missing the top of their skulls leaving their brains exposed...
The re-purposed protocol droids nicely subverted the Robot Buddy trope by, you know, trying to blow you up whilst still trying to be helpful.
"I cannot help you if you keep hiding."
"Where are you, Sir?"
"Did I hear someone calling me?"
"How may I assist you?"
The cargo areas as the scariest levels you'll ever play in a computer game. You forgot to mention that Cargo Bay 2 was full of protocol droids in boxes, and if you walked to close or too quickly they would burst out and give you an explosive hug if you weren't careful. Enough to make anybody jittery. Mix in the things that happen all through the game, ie ghosts, hybrids lurching at you unexpectedly, sentry turrets around blind corners, and the audio logs, and you have an excellent reason for even the word "'Cargo'" giving you a brown trousers time.
In the first level or two there you come across the someone who has hanged themselves; the creepiest part is that the expression of pure terror on the corpse's face makes it appear as if they were more terrified of what was watching them hang than the fact they were being hanged.
On the 5th level you stumble onto landing pads full of dead bodies apparently trying to flee the station, and the creepy droning music that was made just for this area...
And we can't forget the ending of the second game!
Rebecca Siddons: Tommy... What's the matter, lover? (turns out that SHODAN's possessing her)
The Many illusion, where you see a large room filled with what looks like biomass, pulsing and writhing as the Many whispers to you. Not to mention that you can see a thing walking around the room.
What's even worse? You have to fight those things later on.
Very subtle one, but made more powerful due to being rather unexpected. Apart from deranged screams and pleas for mercy, Hybrids sometimes moan 'You're alone'.
Another subtle one, easily missed: Whilst getting out of Cryo B at the very beginning of the System Shock 2, you go through a door, to your left is a vent shaft (first of the game) that you're about to go crawling through, and to your right is an unbreakable window... beyond which you may notice a screaming nurse being pursued by a hybrid...
In a tactful example of Nothing Is Scarier: The Garden room. Lots of greenery, some loot, a body or two, repetitive creepy music... and not one enemy. Your heart will pump faster just by entering the room waiting for another respawn to occur.