- Marine Sandwich may be a villain but her ordeal is tragic. A case of Mistaken Identity costs her her chance of participating in the contest, her attempts to explain the situation lead to her being Mistaken For An Impostor and Getting the Boot twice. By the end of the issue, she crosses the Despair Event Horizon and ends up being Hoist by Her Own Petard in a fight with Pinkie and Applejack. Even though she was a villain, Marine Sandwich was more of a Chew Toy as nothing good happened to her in the story even before she turned insane. This happened because of Poor Communication Kills kicking in. Had somepony listened to her, the rampage could have been avoided. Even worse is that Applejack acted like the rest of the Apathetic Citizens in the story, not even bothering to talk with Marine Sandwich in their previous encounters, or even commenting about her being kicked out in spite of her watching the security ponies commit the deed. By the end of the story, nopony knows Marine Sandwich, only seeing her as a crazy mare that froze everypony with icing. Even if somepony finds out who she was, her career may be as good as over thanks to her psychotic episode.
- Issue 9, involving Granny Apple trying to reconcile the Flim-Flam brothers, who have parted ways over a mare they both had a crush on. Both brothers are miserable wrecks without the other, Flim in particular. At one point, Granny sees him wandering away from the convention and follows, sure he's up to something. She finds him just sitting under a tree, looking forlorn and lonely. It's enough to make Granny feel sorry for him and offer some comfort and advice.
- Issue #14 has the dragons of Dragontown Fillydelphia being unfairly blamed for setting fires. Then there is when Luna becomes frusterated with the case and unfairly takes it out on Spike. Saying she's disappointed in him and he let her down when she had faith in him. The poor dragon didn't do anything wrong. She does later apologize to him though. This could be upsetting for anyone who has had someone take something out on them even if they did nothing wrong and did nothing to deserve it.
- The end of Issue #20 with Luna and Discord. Discord's worst nightmare is a perfectly happy day with Fluttershy and the Cutie Mark Crusaders. He reminds Luna about what happened with Tirek, and thinks that since he's a being of chaos, it's in his nature to eventually betray ponies that he cares about and hurt them when he does. Then at the very end of the comic, Luna writes a letter to Celestia that she realizes she grapples with the same issues as Discord, and wonders if she spends so much of her time alone for the same reason.
- The Genius Loci, Woobie, Destroyer of Worlds house in #34. After its original owners' heavily implied deaths, it crossed the Despair Event Horizon and began abducting other Ponies, desperately wanting to keep reliving the same merriment that said owners frequently hosted. Thankfully, Pinkie and Cheese Sandwich ultimately help it figure out how to Take a Third Option, thus giving it an ok ending.
Tear Jerker / My Little Pony: Friends Forever