* Dana's fate. [[spoiler:Throughout the game, it's shown that despite his faults, Alex does [[MoralityPet genuinely care for his sister]]. On the other hand, her life has been turned upside-down; Blackwatch tried to drag her off for interrogation, she's helping Alex get to the AwfulTruth and finding out some pretty nasty secrets. Then, she finds out her brother has been eating people alive, rightly, she's terrified of him. When he returns later, she forgives him, but still seems terrified. Then she is kidnapped by a Leader Hunter and rendered comatose by whatever Greene did to her. And it's revealed that Alex never cared about her; she was just a pawn in his plans. The player character is a viral doppelganger of her brother; even though he does care about her, he's still a man-eating abomination. And she might be infected...]]
** The clearest moment this all comes across is when Alex comes in, staggering from the parasite, Dana starts pulling up information to help him - and Alex says something he couldn't possibly know. When she demands clarification, he makes an increasingly creepy rambling speech about how he ''needs'' to kill, needs these minds inside him, how ''right'' it feels...all while Dana is backing away from him, looking more and more terrified. ''Finally'' he realizes how scared she is (when he has her backed up against her desk), eases off, looks genuinely contrite and reaches out to stroke her cheek. She won't let him. He leaves. As bad as Alex is, he loves his sister...but he's not human enough to help her.
* The sequel shows James Heller learning that his wife and daughter are dead by the time he returned from a war overseas. As a result, he goes on missions in the Red Zone in hopes of getting his wish: [[DeathSeeker to die]]. FromBadToWorse things go when Alex infected him with the Blacklight Virus, which ''saved his life'' - and now all Heller wants is Mercer's death because of it.
** The virus didn't save his life, [[spoiler: And Mercer had long since said farewell to ethics and decency; Heller was [[PapaWolf more or less justified]] in his reaction and wanted Mercer's death for [[RoaringRampageOfRevenge far bet]][[UnstoppableRage ter reasons]]. Of course, that just brings with it a whole new set of tearjerkers...]]
** There is more to this. Heller was on the phone with his wife who was scared about the infection. She kept insisting that there was something up with Blackwatch, but Heller reassured her that they're specialists and knew what they're doing, that when they said their street was safe, they were telling the truth. Yeah, we all know how pragmatic Blackwatch is. What makes it Tearjerking is Heller talking to his daughter, Amaya, and this little exchange:
--->'''Amaya:''' I miss you, Daddy.
--->'''Heller:''' I miss you too, baby-girl. Daddy's coming home.
*** James Heller was one day away from coming home when he made that phone call. He came home to the body of his wife and his daughter wasn't there -- just her [[EmpathyDollShot stuffed rabbit]], which had ''blood'' on it...
* [[spoiler:The fate of [[SacrificialLion Father Guerra]].]] This man sacrifices his time and safety to help James Heller stop Gentek, Blackwatch, and Alex Mercer. But when Heller pisses Alex off one too many times, [[spoiler:he personally tracks down and guts Guerra. Heller cannot get there in time to save him.]] To make matters worse, Father Guerra was the last person alive that could personally connect with Heller.
* When Heller [[spoiler:finally finds his daughter, along with Dana Mercer, inside the bank vault.]] He rips the door off its hinges to free them, but [[spoiler:Amaya is terrified of her father now. After all, he's ''infected''.]] The way she shies away from him and the look on Heller's face is gut-wrenching.