Please don't list this on a work's page as a trope. Examples can go on the work's YMMV tab.
If you think about it, Rafe "lost" all of his children in a short period of time. Ouch.
Luke was murdered.
Quentin ran away.
Christie got married.
Sukar's "death", poor Irisa.
Christie's and Alak's wedding being called off by Datak.
After Skevur's plot to kill Stahma fails, Stahma decides to bully Alak into dealing with him. As incompetent as he is, it's still hard not to feel sorry for him when he nearly bungles the job, barely manages to kill Skevur, and afterwards, is so horrified by what he's done that he throws up.
It becomes even more tragic in a subsequent episode when Alak learns that by killing Skevur, he's finally convinced his father that he's a worthy successor to his criminal enterprise.
The normally hard bitten and stoic Nolan is literally about to break down in tears when he comes to think that his precious daughter Irisa is going around killing innocent people. Unfortunately, it turns out to be something worse... she is unknowingly infecting people with some sort of tech virus.
Amanda breaking the audience's heart with five words: "The man who raped me."
And then it gets worse. She got pregnant from it, but got an abortion. Connor, who didn't know, though it was his baby that was aborted. It wound up tearing up their relationship, and now that he's dead it can't ever be fixed.
In "Put the Damage On" it gets even worse. Amanda hallucinates a vision of Nolan saying horrible abusive things and trying to rape her, and afterwards she won't let the real Nolan anywhere near her. Nolan's stoic facade cracks even more here; he sounds so desperate when he says, "That wasn't me, you know..."
The long, lingering final shot of "Put the Damage On" is Doc Yewll walking slowly through a silent, empty Defiance, all alone. It's a powerful visual reminder that everyone else in the town has someone. They may not have a good relationship with all of them, but everyone in Defiance has friends, family, someone they love, or at least someone who looks out for them. Doc has no one. Is it any wonder she's willing to cling so desperately to a warped illusion of the woman she loved?
Pottinger sending Churchill on a Suicide Mission, knowing without a doubt he's not coming back. You can tell Pottinger's genuinely affected by it, and even toasts his name later on.
Nolan:Churchill died a hero. If he hadn't gone out there, all three of us would be dead. Pottinger: Would you have sent your Irathient girl?
Berlin actually cared enough about Tommy that she would have gone with him anywhere the E-Rep had a presence, even if the location was a terrible place. And yet everything Tommy is saying is just making things worse, so she breaks off their relationship then and there.
Christie and Alak's breakup in "If you Could See Her Through My Eyes," combined with Christie's cripplingly bad self-esteem issues leading her to cosplay as a Castithan and assume a Casti identity...under the name "Stahma".
In "Painted from Memory," Datak tells Stahma that he never expected her to kill Kenya, and still assumes, even as they're looking for her grave, that she just put her on a landcoach heading out, and that this entire thing is an elaborate fiction.
Datak: I didn't need her dead! I needed her out of the way. Stahma: Don't...don't tell me that I killed Kenya Rosewater for nothing.
And then, later it turns out "Kenya" is actually an Indogene spy intended by Pottinger to be used in a kind of twisted "win the girl" plot with Amanda. Amanda mourning her sister at the end of the episode is bittersweet because she has closure, but also because now she knows for sure she'll never get Kenya back.