The original Little Orphan Annie comics feature horrific, pure white eyes utterly empty of soul or emotion, on every character, for no apparent reason.
In 1970s Marvel Comics, this was Spider-Woman's shtick; her comic's tagline was "To Know Her Is To Fear Her!" She is, biologically, literally part spider, and was raised by Petting Zoo People and Beast Men to boot. When she finally enters the human world, nearly everyone is instantly, instinctively afraid of her, making it extremely hard for her to find work or shelter, and leaving her terribly alone. Still, through tremendous effort, she eventually overcomes this and makes a good life for herself, making for a very inspiring character arc. However, Executive Meddling later put her on a bus for twenty years, and when she was finally brought back into the limelight, this whole aspect of her origin was pointlesslyretconned away.
Scott McCloud's Making Comics had a few pages of faces showing various basic facial expressions as a guide to how that kind of thing works. And they were creepy as hell.
The "Photorealistic" painted style of Kingdom Come and Marvels falls into this sometimes, more so with the latter.
Silent Hill: Sinner's Reward is guilty of this, too.
Alfred E. Newman. Especially seeing his creepy grin pasted onto other popular culture icons.
Fall Of Cthulhu introduced a brand new character to Lovecraft's mythos: The Harlot, a Magnificent Bitch and keeper of all men's secrets, whose giant green head houses a nose too flat and a pair of juicy red lips a little too big. She's a wonderful example of what a Humanoid Abomination would look if it took up burlesque fashion.
Beautie from Astro City fits this trope; she is a living, life sized Barbie doll, so it makes sense.
She's also painfully aware of it, and deeply disturbed when men find her attractive.
The caricatures from the 19th Century political satire magazine Puck can come across as this, on account of the photo-realistic style.
Comic book artist Greg Land only ever draws a few default faces for his characters: orgasm and indifference for the females, and anger and orgasm for the males. It gets really annoying because he tends to use the same faces over and over again.
Actually, Larson makes his people cartoon-y enough to avoid problems. It's only when he tries to emulate the style of more serious cartoons (to parody them, usually) that they get creepy.
Quite a few mainstream comic publishers have been using Poser for some of their comics. It always looks terrible.
