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- Peter Russo's entire story arc:
- Russo slowly breaking down at his laptop, while reading about all angry letters of the people who lost their jobs due to the closing of the shipyard.
- Russo's attempt at sobriety and faithfulness, inspired by Frank, being undone slowly during a conversation with Rachel, culminating in him giving in on both booze and lust after finally getting his life together and getting things right.
- Russo's daughter telling him she and her brother don't want to talk to him when he calls her while drunk.
- Related to the above, the Fridge Horror of Russo's children's last memories of their father will be of them being distant and aloof or just outright not wanting to talk to him. The next they hear of their father, he has died of a supposed suicide. Being 11 & 8 years old, they'll grow up with the feeling that their rejection of their father led him to kill himself. It won't be much more of a comfort if they ever find out he was murdered.
- Russo's children asking whether Christina is coming back because they liked her.
- Underwood's words to a screaming, deranged homeless man trying to get into the congressional office building: "Nobody can hear you. Nobody cares about you. Nothing will come of this." It's the look of utter shock and despair the homeless man gives when Underwood's words sink in.
- Claire's panic attack after meeting her college rapist for the first time in several decades. And Frank's reaction to this, and their conversation later that night...basically everything regarding that situation.
- Everything that happens to Freddy, through absolutely no fault of his own, after getting caught up in the war between Frank and Raymond Tusk. After business picks up enormously after a flattering human interest article is written about him running the Vice President's favorite restaurant over the past twenty years, he blips onto Tusk's radar as a connection to Frank and therefore a target. He releases information to the media about Freddy's criminal past when he was a young man and causes a potential restaurant franchise investor to back out of giving Freddy a huge paydaynote At the same time, Freddy's estranged son, with whom Freddy had just begun to reconcile, violates his own parole after pulling a gun on a paparazzi photographer. In the end, not only does he lose out on owning several franchise restaurants, but he has to sell his own to pay for his son's bail.
- His last conversation with Frank is the biggest example of the sacrifices Frank has to pay for his ambition. After hearing about Freddy's troubles in the paper caused by Tusk and in the middle of a huge marital scandal involving Claire and Adam Galloway, international tensions with China, and everything else on his plate, Frank drops everything and heads to Freddy's apartment to help any way he can, telling the audience that he "does not leave a man bleeding on the field". But Freddy has had enough of the whole mess and wants no part of Frank's offer to help, especially after Frank tells him that he has to distance himself for political reasons. When Frank leaves, Freddy doesn't even call him a friend, just "a good customer".
- Walker's wife phones Claire and calls her a good person as the Walkers are finalizing their departure from the White House, an exit engineered by Frank and Claire. Claire doesn't take it well.
- Rachel being forced to break up with Lisa, the one person she'd managed to forge an intimate connection with since the series' premiere, all because Doug felt disconcerted by the relationship. Worse because when she breaks up with Lisa, she's not allowed to tell her the real reason for it, with Rachel instead saying that she never loved her, sending her over the Despair Event Horizon.
- Lucas' conversation with Janine before he's about to serve his term in prison.
Lucas: He's going to get away with it, isn't he?
Janine: (beat, tears in her eyes) Yeah.
- Basically Adam's entire ordeal in Chapter 22 ends up as this. His relationship with Claire is wrecked due (once more) to the war with Tusk, his professional career will probably be damaged beyond repair, and it's hinted that his fiancée holds resentment at him for complying with the Underwoods' final solution.
- Everything that happens to Megan Hennessey, the marine private who was sexually assaulted. Despite her courage to come forward and help Claire with her sexual assault bill, her manic depression and the stress of events undoes any effort she makes towards recovery.
- President Walker's resignation speech. He was so close to saving his presidency only for him to grasp defeat from the jaws of victory thanks to Frank's letter.
- Michael Corrigan's suicide.
- The death of Ed Meechum when he's killed during Lucas Goodwin's assassination attempt hits hard, considering that Frank saw in Meechum some real, honest to god innocence and naivety. Not the usual kind that he could regularly exploit or manipulate (although he obviously did do it when he first met Meechum), but the kind that he could use as a sort of conduit to let his own hair down and have a little bit of carefree fun, e.g., the baseball throwing or when Frank traced around his hand on the wall. The latter is more depressing when Frank finds out that Meechum's handprint was painted over.
- Lucas Goodwin returns in this season, only to end up dying for his efforts. His noble crusade to finally bring down Frank and his administration, built on the bodies of three people (one of which was his girlfriend) and a multitude of lies, ends up failing when he hits rock bottom and ultimately decides to shoot Frank, as he had nothing else left to lose. Frank doesn't even die from the bullet wound and Lucas inadvertently gets both Frank and Claire, who were at each other's throats, to forgive one another and get back together. Worse his research is dismissed as the ramblings of a "disturbed" man and Dunbar's campaign ends up taking the heat for Lucas' actions. Just when it finally looked like Frank, Claire, Doug, etc. were finally going to answer for their sins...
- Lucas' mental state is worth extra mentioning: at the beginning of the series, he was a smart, clean, respectable young journalist. After Zoe's death, his obsession with taking down Frank starts weighing him down and ultimately gets him arrested for his troubles. When he's finally let out, he ends up working odd low-paying jobs, has to live on the down low in order to avoid appearing on Frank's radar, and even ends up having to perform sex acts on his boss just to get a workable car. Meeting with Dunbar and pleading with her was his last hope but Dunbar inadvertently ends up crushing his hopes when she voices out loud that she wanted nothing to do with him. The tears and despair in Lucas' voice and facial expression drive home the unfairness of how much Frank has screwed him over, which led to Lucas trying to shoot Frank as a last resort.
- If you think about it, Lucas' chance of having a normal life died with Zoe. It wasn't just Zoe's death that broke him though. It was the fact that as a reporter, the truth meant everything to him. He was one of the only people that knew all the Underwoods have done. Yet there was no way to make anyone believe him. Everything in his life was stripped away from him in the pursuit of exposing the truth. Zoe, his job, his freedom, everything was taken from him. Hell, even his name was taken away from him (due to the witness protection program.) He ended up with absolutely nothing left to lose.