Carol slitting her wrists after breaking up with Tyreese, who was given oral sex by Michonne, and how it leads to Tyreese and Rick fighting and permanently testing their friendship.
Volume 7: The Calm Before
Carol's suicide after gradually being broken mentally. Everyone watches on in horror as she walks into the zombie's reach, and Sophia's vacant stare afterwards is particularly upsetting.
Volume 8: Made To Suffer
In general, The Governor's attack on the prison and the casualties suffered. Most notably Hershel desperately dragging a shocked Billy to safety, only for Billy to be shot in the neck, leading to Hershel losing the will to live and pleading for the Governor to kill him. Similarly, following the Governor's orders, a soldier named Lily Caul shoots and kills Lori, who falls to the ground and crushes her baby daughter. Unable to cope with what she's done, Lily murders the Governor in cold blood. The final panel of the volume is Rick and Carl alone, tearfully embracing.
Volume 10: What We Become
Abraham, Carl, and Rick sitting beside the car talking. From Abraham's story In which several people in the first group he's joined up with raping his wife, daughter and two other girls while making his son watch. When he finds out, he goes on a Roaring Rampage of Revenge which scares his family enough to cause them to leave. He goes after them, and when he finds them, they'd been attacked, with his daughter zombified, forcing him to kill her. Then he joins up with Rosita and Eugene's group, three people try to take some supplies and leave, forcing him to kill them. He then sits crying, wondering if he's become a monster like the zombies around them. Rick then tells how he killed Dexter during the roamer fight, and how he ran over Martinez with the RV before beating him to death. Rick then says that what they're doing is necessary to protect those they care for, and how he worries about what would happen if Carl knew. And if that weren't enough, Carl talks about how he shot Shane in the neck to protect Rick, and how he wished he could kill the man who killed Lori and Judith, as well as help kill the man who tried to rape him. The scene ends with Carl and Rick embracing in tears while Abraham sits silently next to them.
Morgan saying good-bye to his zombie son.
Volume 11: Fear The Hunters
Even though they were cannibals, Chris' group needed to survive. And the look on his face before Rick's group kills them was just heart breaking.
Volume 14: No Way Out
Morgan talking to Carl on his deathbed. Made even worse when he confuses Carl with his son. Guy just can't catch a break.
Volume 17: Something To Fear
The absolutely brutal death of Glenn at the hands of Negan and his baseball bat as several of the other survivors are Forced to Watch.
Volume 24: Life And Death
Alpha kills Ezekiel and Rosita (who was pregnant with Eugene's baby) by luring them out into the open by posing as a friend of Rick's. The worst part is that both victims wanted to rebuild their relationships with their lovers before getting decapitated. There heads are latter seen on pikes outside of Alexandria, where Rick's group mercy kills them along with the other victims of the Whisperers.
The massive funeral montage in issue 146, which shows the friends and family of the killed characters grieving and screaming at Rick to do something about what happened.
Rise Of The Governor
The Road To Woodbury
Josh telling Lilly about the fate of his mother. When he got home from work he found her remains spread out across the table at his house. Apparently, she mistook the zombies for starving homeless people and let them inside herself.
Josh's death. Its extremely sudden and happens right after he and Lilly have a falling out after she told him that she might not actually love him. What makes it worse is just how senseless it was, he didn't get attacked by a walker or suffer an accident, no. He died because he refused to hand over a bag of supplies he found to the butcher, who was already working him like a dog and driving up his debt to him. The kindest, nicest person to survive the zombie apocalypse and he gets shot in the back of the head out of petty greed.Damn.