The very first issue ends with the Pride murdering a young woman in cold blood as the kids look on from above.
In the vampire arc, the kids learn the hard way just how green they all are as Topher, a Smug Snake vampire, beats them all up. He's defeated only because Karolina begged him to feed on her in exchange for sparing her friends, and she just happens to have solar-charged blood.
The kicker? Karolina wasn't even aware of that particular bit about her blood. She was fully convinced it would kill her (she probably never thought it would turn her due to her being an alien and whatnot), and she was ok with it, because she didn't want to live in the same world with people like Topher and their parents.
In the "Escape to New York" arc, the Runaways' ally Dagger is attacked (and possibly sexually assaulted) by someone impersonating her partner Cloak. And it turns out that the culprit was a hospital orderly who had access to her room...
In the "Live Fast" arc, Chase temporarily turns against his teammates in an effort to resurrect Gert. The scary thing is how competent he was at being a villain, easily hobbling Nico and Victor and leaving the rest of the team scrambling to catch up.
Also worth mentioning is his kidnapping of Lotus and forcing her to help him find the Gibborim and ask to resurrect Gert. While Lotus wasn't totally innocent, it still was creepy to see him threaten her with Old Lace and seem to seriously contemplate sacrificing her. The cold way he tells her to "set [herself] on fire for all I care" after they part ways is also pretty chilling, considering how he'd never shown anywhere near that level of venom towards anyone before.
In this arc its also learned what happens to the sacrifice victims when the Gibborim eat their souls...they are completely erased from existence and everyone that knew them forgets all about them.
During the Civil War tie-in miniseries, SHIELD declares war on the Runaways (because the agency's been taken over by Maria Hill.) In their opening salvo, SHIELD shoots up Victor, tearing his body apart in a horrific manner. As a follow-up, they send a genocidal alternate-universe Kree soldier who snaps Xavin's neck and then captures Xavin and Karolina, as well as Wiccan and Hulkling of the Young Avengers, and sends all four of them to a black site where they're tortured in front of each other by a fat, ugly, mind-rapey creep.
Said torture is vivisection. Which it's implied he performed on a still-conscious Wiccan and is attempting on Hulkling. Because of Hulkling's healing factor, his organs keep shifting and the cuts on his body keep closing up, meaning that he's repeatedly sliced open. The scene opens with this, as an incredibly unresponsive and dazed-looking Wiccan repeats over and over "I want him to go to sleep, I want him to go to sleep, I want him to go to sleep..." (the doctor realized his magic only works if he can hear the commands, so he plugged Wiccan's ears). Oh, and Xavin's body is left on the floor for no reason other than to psychologically torture Karolina.
In the final arc of the second series, there is Mr. Prast. We only see him on-panel once, but the way Klara's eyes keep darting away and the way her voice trails off when she tries to talk about what he does to her, and the ever-growing collection of bruises on her face all convey that Mr. Prast is a very, very bad man.
The Third Series:
In "Mollifest Destiny", Molly is kidnapped by a third-rate supervillain who tried to challenge her parents years earlier... and was psychically forced to watch as his entire team was slaughtered by the Hayeses. And then they left him locked-in, unable to move, for seven years, to the point that his eyes are permanently bloodshot and he requires the use of Powered Armor in order to move.
The last arc begins with a party, albeit a kind of depressing one... and then something crashes into the Runaways' house. Right off the bat, Old Lace is dead, and Klara is injured. And then Klara wakes up, scared, bloodied, and confused, and lashes out. The last panels show the beach erupting in a forest of vines. Beware the Nice Ones, indeed...
The Fourth Series:
The Stinger to Issue #3: Molly's grandmother is keeping someone locked up in her basement.
Everything about Mollys grandmother: The way she not only seemed unfazed by her daughters relationship with her foster son but its implied actively encouraged it, the way her cats have the exact same eye glow as Molly and her parents, the fact she gave Alice and Gene their powers, meaning she experimented on her children. That she plans on doing the same to Gert makes it worse. And wants Victors genetic material as well due to his being a cyborg.
In Issue #12, as Nico prepares for her date with Karolina, she suddenly has a hallucination that the Staff of One is ripping itself out of her body. It comes out of nowhere, and there's no explanation for it, and afterwards, she suffers an anxiety attack.
Nico's powers seem to grow more and more lethal with each arc. In just the first issue of volume 2, she splits the supervillain Wrecker into several pieces,while keeping him alive. At the end of volume 2, she essentially traps the Yorkeses in a timeline where they're doomed to witness their future selves' evil and foolish actions, unable to change anything, until their deaths.
In the post-Whedon arcs, Nico becomes increasingly comfortable with using her magic on her own teammates - attempting to stop Xavin's heart after believing that the latter had turned against the team, trying to use a spell to compel Chase to tell the truth, and, in the last story arc, using what amounts to Mind Rape on Klara because the poor girl is suffering from a panic attack and her crying is getting on other people's nerves. And then there's the short story from Breaking into Comics The Marvel Way, "It's Not Lupus", where Nico loses her temper at Molly and Chase and accidentally poisons them with magic.