Miko Miyazaki's slide from holier-than-thou Knight Templar to a Tautological Templar has her murder her lord, lose her Paladin powers, and accidentally kill herself in fulfilling what she had decided was her divinely ordained destiny. The ghost of her order's founder tells her that her efforts were... adequate... but not worthy of redemption, which she accepts with uncharacteristic grace as she dies. It's still debated whether she deserved it.
In strip 830, it's really hard not to pity Tsukiko — an unrepentant Card-Carrying Villain who sold out her own city to Xykon — when Redcloak usurps control over her wights, who she'd treated like her own children, to prove that undead are little more then automatons for necromancers of any stripe. And then he has them drain her to death. And then eat her. She was a sick, twisted, self-confessed necrophiliac who was obsessed with Xykon because every living person she ever met in her entire life treated her like crap. What puts her solidly in Alas Poor Villain territory is that she really and truly loved him, and only died because she discovered concrete proof that Redcloak is manipulating Xykon, and that the MacGuffin they're after won't get Xykon the power he wants. The point really gets hammered home when the only person to mourn is the Monster in the Darkness, who points out that in the end, Tsukiko just wanted to be loved.
Demon-roach: So what? Who cares? Monster in the Dark:Exactly. That's why I'm sad.
Nale's death in 913: Independent has caused some of these reactions. Nale is a petty, selfish mass-murderer, but hearing his anger about being treated like a tool by his father, and refusing his father's help to his face shows that he has balls, only to get stabbed by his own father. Plus Elan's reaction...
Subverted when a reanimated Crystal is dumped into lava: three panels of silence, followed by brunch.
Whenever Oasis dies in Sluggy Freelance, it's treated with sadness, even when she's been in full-on Ax-Crazy, Stalker with a Crush mode, since we know she's only like that because Dr. Steve Brainwashed her. However, as Oasis becomes more heroic and we learn she'll always come back from being killed, this has faded.
Violent Glaswegian Dougie in What the Fu suffers a breakdown from the revelation that he's not actually Scottish. Zac almost feels sorry for him, except he's "still a murderous psychotic bastard".
Vriska Serket, who had spent the entirety of Act 5 Act 2 getting closer to John and finally admitting that she wanted to try living a normal life. She was killed by Terezi in order to prevent her from fighting Jack, which in an alternate timeline got everybody except Vriska and Aradia killed. Her final message? Telling John that if and when they finally do meet, she'd like to go on a date.
Courtyard Droll, Jack's clueless underling who fails at being evil, which gets his superiors pretty annoyed with him. When he finally manages to follow one of Jack's orders to the letter (Jack had ordered him to kill Jade, something Jack himself couldn't do due to his Undying Loyalty from Bec's prototyping), Jack snaps and kills him. Thankfully the Scratch brings him back. Sort of.
Snowman is a Jerkass, but it's hard not to feel bad for her when the Doc Scratch-influenced Spades Slick shoots her dead at the end of Act 5, especially since she had just saved his life a few moments before. Furthermore, she requests and welcomes her own death as an end to her eternal servitude to Lord English.
Ephsephin is an Ineffectual Sympathetic Villain who suffers more and more abuse as the story goes on. He becomes even more sympathetic when Word of God says he was a failure at life who was obsessed with over how he couldn't provide a better life for his mother. The only reason he signed up with Starfish was to get a big enough payoff so that she wouldn't have to keep breaking her back working. After he gets grievously wounded by Jivi and begs Starfish for a doctor, Starfish merely smiles, then bashes his head in with a whiskey bottle.
Stockyard has a rather drawn-out and horrific death, involving many sharp objects and ultimately decapitation, and just when we're starting to get the idea that he might have some redeeming qualities (he chases Starfish away from Sette, and is disgusted and pissed Starfish used kids to smuggle the silver). Anadyne also unwittingly accelerates his death by trying to save him as he pleads for help.
Karl, despite being an utterly contemptible Smug Snake, suffers a truly gruesome fate, being tortured, mutilated and sexually assaulted by Ruck. Even Ashley describes the scene as "miserably horrible".
Tobun in Penny Arcade's Cardboard Tube Samurai storyline, is implied to have become a Death Seeker after being compelled to commit atrocities. Fighting the CTS hand to hand, his last words are "before this moment, did I ever see the world?"
Dragon Ball Multiverse: The first Cell Jr's death by his own father's hands. Especially after he had a Hope Spot of becoming more powerful.
At the Grand Finale of Errant Story, Ian just keepsrepeating "I just wanted to help." Despite a personal body count in the thousands, he's quite serious. However, it doesn't keep him from getting his brains blown out.
Kalki in Drowtales spends the majority of her screentime either acting like The Fake Cutie or inflicting serious harm or brutal deaths on other characters, including stabbing the hand of her own half-sister and nearly killing her by chopping off her arm the very first time they meet, but the way her mother Snadhya'rune, whose neglectful parenting was at least half the reason she became as twisted as she did, coldly kills her and tells her she has outlived her usefulness firmly puts her into this.
El Goonish Shive: As nasty a person as Sirleck was, his demise is painted in a surprisingly sympathetic light, with Magus in tears over being forced to kill in self-defense the closest thing he'd had to a friend in years.
The death of Dr. Tarsus Beetle is so upsetting to the protagonist that it triggers her breakthrough even though he was killed in apparent self defense. It helps that the true horror of his actions and the fact that he was trying to kill Agatha rather than Gil only come to light after his death has been mourned for a chapter.
The death of Anevka Sturmvoraus - or should we say, Clank-Anevka's realization of "her" death. Even as he's spelling her end, Tarvek is having a hard time bringing himself to do it and tell the truth to her.
. It's still debated whether she deserved it.