- Nate reuniting with his long lost brother, Sam, towards the beginning of the game. They spend hours catching up, with Nate inviting Sam to have dinner with him and meet Elena.
- When presented with the opportunity to restart their search for the lost treasure of Henry Avery, Nate wants to Opt Out, saying he's done playing treasure hunter. In exchange, he tries to offer up someone from his contacts list that he knows could handle the job. Sam immediately turns it down, saying no one has your back better than your Bash Brother and Nate winds up agreeing. It's a poignant moment that emphasizes how strong Sam and Nate's bond is.
- Most of the interactions in Nate's house—looking through a photo album showing Nate and Elena's wedding on the beach (featuring a proud Sully tearing up); Nate warmly muttering "Miss you, pal" as he looks at a picture of himself with Tenzin at Nepal; trying to beat the high score on the "TV game thing"... which is a short section of the original Crash Bandicoot (1996) on Elena's PS1.
- The reason why Sam lied to Nate; he just want to share another adventure he saw that they inherited from their mother together.
- Most poignantly, when all is said and done, for all of Sam's flaws, and the hell he's inadvertently put his brother through, Nate realizes Sam is still too good a man to leave behind, and fights off Rafe and figures out a solution (sink Avery's ship with a cannon) that allows him to free a trapped Sam.
- The Reveal in the epilogue where you find out that Nate and Elena have a daughter, Cassie, who is named after Nate's mother. After she discovers their mementos of their previous exploits from the last three games, her parents decide that it's finally time to tell her everything. Plus, Cassie seems to have inherited both her parents' sharp wit.
- When Elena and Nate stumble upon the gathering of the poisoned Founders, sans Avery and Tew, Nate starts going off into an excited ramble about their findings, and Elena looks on. The scene is set up as a near mirror to the beginning, when Nate blanks off into space while Elena talks about her own work, only Elena is staring at Nate. There's sadness in her eyes, but also a glint of familiarity and love. And there is a small smile on her lips that only grows more sure until Nate catches her staring. For all that he's done, and for every right Elena has to never forgive Nate, she still loves him—and that this excited rambling was one of the reasons why she fell for him. And this time, Nate pays attention: he apologizes to her for everything.
- The fact that, for all his flaws, Sam does genuinely love Nate a lot. He's always checking to see if he's alright, helping him when he's in trouble in a fight or catching him when he falls, and he's been shown to be willing to take a bullet for him twice.
- Blink and you'll miss it, but when Rafe threatens to shoot Sam on the cliff, despite the fact that Nate has just found out Sam has lied about whole thing, Nate tries to calm Rafe down and edges closer to Sam with every step, almost as if he's trying to get between Rafe and his brother.
- After Nate is found by Elena, he asks her why she came and she responds she had seriously considered not bothering this time and that her husband's recklessness/lying had gone too far. But in the end, she did because there's still a bond there. Afterwards Nate monologues that he married a girl as talented as himself and almost squandered it over some petty treasure.
- The last scene in the epilogue: Elena puts the photo of her, Nate, and Sully that Cassie found standing beside the treasure they found at the end of the first game. In the book besides the Photo of young Nate and Sam, right above the word SIC PARVIS MAGNA.(Greatness from small beginnings) Reminding us of both Nate's in universe humble start, and our first unforgettable adventure with him and the team.
- A very small example, but when the old lady finds a younger Sam and Nate going through her stuff, she points a gun at them. When the old lady points the gun at Nate, Sam's big brother instincts kick in and he steps in front of Nate, telling her to keep her gun pointed at him and not his brother. His care carries on even in adulthood, when he takes a bullet for Nathan when Rafe attempts to kill his brother. It really shows that even with all of Sam's flaws, he truly does care for Nathan.
- There's also the old lady's temporary shock and immediate joy upon realizing the two boys in front of her are the sons of the woman she worked very closely with. Her attitude towards them after the realization is rather grandmotherly, as she tells the two of what a great woman their mother was.
- Another small example, but Nadine and Sully's interactions at the black market auction certainly count. Even though Sully had a run-in with her organisation in the past - an encounter in which he was implied to have been the victor - Nadine not only shows no hard feelings towards him, she happily talks, jokes and has drinks with him as if he's an old friend. And Sully apparently trusts her enough to tell her about Nate, as well as one of his past adventures.
- In the epilogue Cassie can find a picture of Elena and Sully enjoying a beer on the beach. It's nice to see that after so long, Nate kept his promise of keeping in touch with his old friend and father figure.
Heartwarming / Uncharted 4: A Thief's End