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- City of Heroes has some sad moments for a bright, fun game of playing superhero (or supervillain).
- The Faultline arcs. They open in an area where hope is being reclaimed; an area of the city that had been devastated by a city-shattering earthquake by the crazed earth-controlling villain Faultline is slowly being rebuilt after the horrors of the Rikti Wars. You gain a cheerful, ditzy sidekick, Fusionette, for a while, and her more sombre, but still decidedly Kid Hero-ish boyfriend... Faultline? As you explore deeper into the past of the villain, the zone, and the hero named Faultline, cracks appear, and the mystery deepens. Eventually, you discover that the first Faultline had been a hero, one of the city's best and brightest. But one of his enemies, PsiCurse, had created the Psychochronometron, altering the timeline and making him into a villain to try and turn his foe into an ally. Unfortunately, PsiCurse' knowledge of Faultline was incomplete, and the resultant temporal stresses drove Faultline mad, making him lose control of his powers and killing both PsiCurse and Faultline's closest friend, and setting Faultline down the path that would orphan his young son, Jim Temblor, and leave him torn for much of his life, with two sets of memories in his head. Thankfully, you can get to the bottom of the mystery, and have it end with Jim Temblor taking up his father's mantle to make Faultline a hero's name again...
- The Dark Watcher's aptly named 'The Horrors Of War' arc. mainly the death of Lt. Sefu, but also the truth behind the origins of the Rikti War.
- Seer Marino's arc, "Oh, Wretched Man!" She asks you to find out what happened in the operation that claimed the lives of her brother, Paolo, and their friend, Belladonna Vetrano, and you discover that Paolo survived but was horribly mutated, and Vetrano died and is now a ghost. They're Wretch and Ghost Widow, respectively.
Vetrano: I died worrying for Paolo, and I will care for him as best I can as long as I exist; it's part of what makes me exist. But by the same token, I also cannot give him up. And though I've tried to make him go, he will not leave my side until he thinks I am safe. We are bound together, protecting each other in our strange half-lives. Tell Pia I'm sorry, but I cannot give Paolo back to her. All I can do is try to protect him as he protects me.
- You call THAT the tear jerker?! Here's what Paolo had to say at the end of the finale - "Wretched words"
In halting sentence fragments, the creature that was once Paolo Marino thanked you, and tried to explain something:
"Wretch thank, Wretch thank. BAD 'rachnos try hurt. You help. You okay. You been near Ghost Lady. Can feel it. So Ghost Lady okay. Ghost Lady told me it all be okay. She so sad, so sad, but she say it all be okay.
I remember. Remember when I was Paolo. Remember when I had job protect Ghost Lady before she Ghost. I remember fire, and pain, and after. I live, and she live, in a way.
Job not over. Not over 'till she finally safe. 'Till she at peace. Tell Pia sorry. Can't go back. Won't go back. Not till job done.
- Aaron Walker, and his last, best final program.
THIS IS THE LAST, BEST, FINAL PROGRAM BY AARON WALKER HIMSELF.
EVEN IF PRAETOR BERRY KILLED HIM, HE'LL NEVER BE ABLE TO BE BETTER THAN WALKER.
REMEMBER TO TELL THE WORLD. BERRY IS A LOSER. AARON WALKER WAS THE MAN.
- The end of Special Agent Jenni Adair's arc.
Your Doppleganger: I knew...you would show up... I would've done...the same... But this...has to be done...only one of us...has to die...today.. This is...the only way...to save this world...from what's beyond...that portal... Goodbye...Character... It's up to you... ...you have two worlds...to defend now...
- Worst part is that if you are really fast you can get to them right before the building blows up.
- Infernia (and Glacia): superhero sisters who sacrificed themselves to stop the Rikti, only to survive in the Rikti homeworld and eventually be rescued. And then, nine times out of ten, the 'heroes' rescuing her will abandon them to be killed by the Rikti, since completing this particular mission isn't required to complete the task force.
- The end of Who Will Die part 5, where Statesman dies.
- Everything that was to do with First Ward. At best the conclusion is a Bittersweet Ending but YMMV if it's this or a Downer Ending.