The hologram of the Soveriegn. It's like some weird live action/CG/animation hybrid that doesn't quite move like it should, and it's unsettling as hell, even if what he's saying is hilarious.
The Reveal in What Color is Your Cleansuit, that the college interns are mutating into monsters, except for the green suited ones. When Sargent Hatred hears they only eat "Student Green" he thinks its a vegetarian diet, but he soon witnesses first hand that "student green" refers to the green suited people. Bonus points for being a Shout-Out to Soylent Green
Sargent Hatred: Oh my god...it's people!! student green is made out of people!!! (cuts to him being carried off by four other mutants apparently oblivious to what's happening to him) WE GOTTA STOP THEM SOMEHOW!!! WE GOTTA TELL DOC!!! IT'S PEOPLE!!! STUDENT GREEN IS MADE OUT OF PEOPLE!!!!!!!
The Investors took a huge step in this direction in "O.S.I. Love You." We already knew that nothing can touch them, they can float through floors and walls, and carry people with them. That means they can take you and kill you the moment everyone's back is turned. Oh, and now they can shapeshift and flawlessly imitate anyone. They keep the Guild running smoothly and do a damn good job ensuring that no one snitches.
To help you understand how terrifying they are, there is an example of how freaked out Monstroso got when he saw a glimpse of them when he was being interrogated by Brock Fucking Sampson. Note: Monstroso has gotten his ass kicked by Brock at least twice and the second time has taunted him by having sex with the love of his life in front of him, surrounded by OSI badasses and knowing that Brock's going to take it out of him, but he still does it just to piss him off. Yet at the mere glimpse of one of the investors he panics, runs all around the room, and knocks Brock out by accident: by flipping the table he was being interrogated at on top of him and running over him a few times just trying to get away from the investors. And that's not even going into the pure paranoia fuel these guys ramp up by just using their powers.
Myra has Dean tied up. So she can shove him up her vagina and give "birth" to him which is already scary in-and-of itself, but made even creepier by the fact that earlier she told him to get undressed and "show mom that handsome new body."
Despite being bat-shit insane, Myra apparently turned an entire insane asylum and a few guards into her obedient cult. Through sheer willpower. When they snap out of it, it's treated as though they were breaking out of hypnosis or brainwashing. It was just Myra. Hell, she even managed to convince Dean to follow her. True, he wanted to bail the moment he was actually with her, but she still got "done-with-this-shit" Dean under her thrall.
Hell, Myra in general. Her insanity is not really played for laughs and she really comes across as dangerously psychotic.
From The Stinger of Bot Seeks Bot: if you're on the Guild's master Council of Thirteen, have ever been in the Chamber Sub Rosa, or anywhere close to the innermost workings of Guild society, guess what? The Revenge Society is WATCHING YOU!
The flashback of M.U.T.H.E.R.'s attack on Jonas' state-of-the-art fallout shelter. As the members of Team Venture are giving orphans a friendly guided tour of the shelter, M.U.T.H.E.R. unleashes some kind of psychotropic gas onto the track, sending them all into blind frenzies. The Action Man sees thousands of bugs crawling out of his clothes, Col. Gentleman sees himselfgetting a blowjob from a strange creature and begins desperately scratching at the walls to escape until his fingers bleed; which is all to say nothing of the dozens of hallucinating, screaming children running around everywhere..oh God, the childrens' screams...
Whatever it was, the alien that killed the Grand Galactic Inquisitor really looked like was this in-universe for all present. The sight of it horrified even Brock, and everyone nearly crapped their pants; except for Ned, who crapped his pants.
The deformed Dean clone is clearly insane. However, it just gets worse when he treats everything like Dean does. Listen to how he says, "there's no more left", as in, there's not more clones for him to kill and skin to get the materials for his "super secret project" read as a Genuine Human Hide. It complains about there not being enough left as if he's referring to someone eating all of the cake. He sounds so innocent for a madman.