- The story of Gonzalo "El Emisario" Yana where he is the deeply devoted to his grandfather, El Yayo and would do anything to please him. The Ghosts proceed to decimate the cartel's production and plan to Blackmail him into turning on his grandfather. Instead, Gonzalo is Driven to Suicide as he had Undying Loyalty to his grandfather preferred death to offending him. Worse, it does nothing and El Yayo is forced to pick up the slack.
- The "Good Ending" of the game where El Sueno is given full immunity for his crimes in exchange for his cooperation against the other cartels and terrorist organizations. He is then going to be "cut loose" and start all over again. It renders all of the sacrifices and deaths in the story largely pointless.
- A more personally tragic version happens in the "bad" ending with Agent Bowman, predicting the above, executes El Sueno and is arrested for murder.
- The revelation Ricky Sandoval is behind the embassy attack. He framed the cartel and got himself tortured to death in order to get the American government to intervene in Bolivia's situation.
- El Gringa's entire story. Misused by the CIA and forced to work for the cartel, she tries to do a bit of good with the rebels then is captured by the Ghosts. Karen Bowman takes an immediate and immense dislike to her, threatening her with Prison Rape. While she manages to survive the cartel's retribution, her fate is unlikely to be a good one.
- El Boquita is a ruthless Santa Blanca underboss who has been trafficking since he was a child. However, it's hard not to feel for the guy as while you're tailing him, he makes a phone call to his daughter and says how much he loves her as well as the fact she can have a puppy when he gets back from delivering billions in cash to Mexico. This is Retirony for him as you're promptly given orders to execute him. He manages to survive only for Nidia, his one true love, to cut his head off in a failed attempt to placate El Sueno.
- The crossover DLC has Sam Fisher realizing he is the last member of the covert op old guard, as an unseen character meant to refer to Snake from Metal Gear retired. While it's presented as a meta gag, his reaction is of genuine sadness, and Metal Gear fans in the audience felt the same way. It gets even sadder when you remember that Syphon Filter had ended years earlier. Metal Gear, Syphon Filter and Splinter Cell were all seen as the trio of stealth-action games in their prime, but Syphon Filter went first, then Metal Gear lost Hideo Kojima and had its newer installments be met with much backlash, with fans saying Metal Gear as it once was is no more. Sam's reaction to hearing the news has more weight with this in mind; it really is just him now. Not to mention he's older than in the past games, meaning it's possible his own time may come to a close soon.Karen:You look like you've clocked a few miles since we last spoke.
Sam:Yeah a few, I've heard they don't make them like me anymore.
Sam: There was this other guy though, Army infiltration, he wore...a bandanna or something.
Karen:(nods) I heard he finally retired.
Sam: (skeptically) Really?
Sam: (utterly crestfallen) Then it's only me...
(long beat as Sam stares painfully into space)
Tearjerker / Ghost Recon Wildlands