- 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?
- The continuing on to the illusion is also emphasis because for one brief moment, you see Yewll gripping the air at the side of her waist, as if holding on to someone's hand.
- On the same regard about Doc Yewll, her remembering that Lev was dead. Her reaction at that moment is heartbreaking, as you can see the anguish and pain at remembering the loss.
- 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.
- In "Doll Parts," Irisa and Nolan's interactions are heartbreaking. Irisa accuses Nolan of corrupting her as a child, teaching her how to fight and kill people and questioning whether he ever really loved her or if it was just fun for a racist soldier to turn one of his enemies into his pet. For his part, Nolan is convinced that this isn't Irisa talking, but the influence of the Irzu AI embedded in her, but he doesn't deny his flaws.
- Poor Amanda, in the space of a month she lost Kenya, her biological sister who she finally accepts is dead. Then she loses Deidre who is also murdered. Deidre who looked up to Amanda as an older sister. And during the investigation, Amanda starts to realize that she was the one who indirectly caused this mess, by encouraging Deidre to fight for this mystery man she's been telling her about. Amanda didn't realize that Deidre was talking about Alak Tarr, or the level of drastic action Deidre was willing to take.
- At the end of the Episode Amanda puts away the badge knowing that there will be no justice for Deidre. Who few if any will mourn. An innocent and dying man allows himself to die in a prison cell so his daughter will have a future. And Tommy is left lying on the ground bleeding to death after Irisa stabbed him, despite him embracing her and trying to convince her to come back to him and Nolan.
- "All Things Must Pass": Tommy dies, despite Nolan's heroic efforts to save him. Nolan has a small understated breakdown when he realizes what's happened, weeping bitterly alone in the woods.
- Its get worse when you realize that Nolan spent nearly two days, and two nights getting Tommy to Defiance . Only to have Tommy die just before they get there. In the end Nolan could have just walked to Defiance to get a roller, and come back for Tommy's body. But despite being exhausted he continued on, dragging Tommy's body back to Defiance. Because Nolan promised Tommy he would get him back home.
- After Nolan has dropped off Tommy body at the Defiance entry checkpoint where Berlin and the perimeter Guards are stationed. Nolan staggers away as a shocked Berlin kneels over Tommy body. checking for a pulse and finding none.
Berlin: How, Nolan?!
Nolan: There's something inside Irisa.
Berlin: Did Irisa kill him?!
Nolan: She's not herself.
Berlin: Did Irisa kill Tommy?!
Nolan: ( In a voice that is equal parts rage, guilt and sorrow} YES!
- As he staggers away in despair we see brave, strong and confident Berlin tenderly caress Tommy's face. Then quietly she begins to break down weeping.
- "I Almost Prayed": Freed from the Kaziri's control, overwhelmed with the knowledge of all the lives she's destroyed Tommy's not least among them, Irisa begs Nolan to give her his gun.
- "The World We Seize"/"The Last Unicorns": The statuses of the McCawley family by the end, as if things couldn't get any worse for them.
- Quentin gets shot in the head by Rahm Tak.
- Rafe is riddled with bullets while trying to save his daughter and grandson.
- Christie deliberately pisses Rahm Tak off to keep him from finding Luke, then dies of a Slashed Throat at Stahma's hands as part of a Sadistic Choice.
- Baby Luke is spirited away by Pilar once again.
- "Dead Air":
- There's something oddly poignant about "George" the Bio-man and his story about his three-legged dog.
- More traumatically speaking, Amanda realizing that Pottinger was her rapist.
- "History Rhymes": Nolan's back story before and during the Pale Wars and the effects on Irisa. Particularly the reveal that one pivotal night in their relationship was not the turning point Nolan thought it was.
- "Where the Apple Fell": As awesome as the payoff was, seeing Datak break down during Nolan and Alak's Reverse Mole routine is gut-wrenching. As horrible a person as Datak Tarr is, he loves his son, and watching him beg for mercy is difficult to watch.
- In "My Name Is Datak Tarr and I Have Come to Kill You", Nolan is left powerless to watch as almost all of his militia, including the kid Zero, are vaporized by a grenade.
- "Ostinato in White" is composed mostly of this when it delves into Nolan's psychological state after the loss of the militia.
Indur: I don't want a broken rifle! I want my son! [...] Can you give me that?
- His first segment has him follow up Amanda's inspiring speech at the memorial with a stumbling, awkward eulogy that's a complete 180 from his badass speech in the previous episode. It's clear that Zero's father's grief has mixed with his own and completely overwhelmed him.
- He becomes obsessed with making amends with Zero's father and shows up at his house with his son's rifle, only to be held at gunpoint by the grieving man.
- Later, he gets blackout drunk and has a nervous breakdown in front of the memorial. The viewer is treated to flashbacks of every minor character who trained under Nolan and died in that tunnel, and it's clear that even though the viewers were only acquainted with Zero, Nolan felt every loss.
- To top it all off, he later returns to Indur's house, only to find that he has been Driven to Suicide.
- "When Twilight Dims the Sky Above": The daughter of the ambassador whose death ignited the Pale Wars is herself killed due to Nolan's delusions.
- "Of A Demon In My View": Kindzi betrays, tortures, and ultimately murders T'evgin.
- "The Awakening":
- Datak taunting Yewll and pleading for death, no longer able to stand waiting for the Omec to devour him. Granted, it was all part of his plan to escape, but there seems to be genuine emotion behind his words.
- At the end of the episode, Kindzi storms into Alak's house, brutally murders Andina, knocks Stahma unconscious, and rips baby Luke away from Alak's arms while he tearfully attempts to resist.
- The series finale:
- As Yewll orders Datak and Irisa to plug an increasing number of tubes into her to grant her more control over the Omec ship, they begin to realize that it's killing her, but Yewll insists that they keep adding tubes, assuring them that she never expected to survive the mission anyway. When the time comes for the final tube, Irisa can't even watch, and Datak hesitates and insists on making his goodbyes first.
- With the ship about to blow up, Irisa decides that she can't go through with killing the Omec, and insists that Nolan find another way. As Yewll informs them that it is theoretically possible to vent the built-up energy into the engines, at the cost of being shot blind out into the galaxy. Nolan agrees. It looks like he and Irisa are about to head off on a new adventure, but as they share another father-daughter hug, Nolan tazes Irisa and throws her into an escape pod; on the off chance that the plan fails, he wants her to live. The plan works, Nolan is sent millions of light-years away, and all Irisa can do is console herself by imagining that her father is off having adventures in space.