What happened to the Sewer Gators for being in the wrong place at the worst time. Pete gets decapitated by a crazed Mia while attempting to save Clancy, Andre gets killed by Jack and his body tossed beneath the Guest House to rot, and Clancy is pulled into one of Lucas' many death traps solely to die a pointless and horrific death by being burned alive.
Not entirely pointless though in that Clancy's video of his own death helps Ethan survive the same death trap later.
Clancy being forced to play a Deadly Game of blackjack against another kidnapped victim, Hoffman. Both men know that the only way to get out of the game alive is to "win" and doom the other to a horrible death.
Hoffman is a father who just wants to get home to his daughter, Melissa. The moment when he quietly promises to win the game to see her again makes it quite painful to beat him.
The knowledge that no matter who wins, they are doomed, as they will be forced to play the Birthday Party with Lucas.
What happens when you finally win the game. You think Hoffman's been dead this whole time from being seemingly electrocuted to death in the previous round and that Lucas has been using his body like a meat puppet. He's not. You now get to witness him waking up to the horrible sound of a saw getting closer to his face, desperately struggling to break free and pleading for help for about 5 seconds before the saw cuts his head in half while he dies screaming and choking on his own blood.
The way Ethan's first fight with Mia (or second, since the technical first one is just to teach you how combat works) ends is in context pretty rough. Ethan stabs her in the neck with an axe just in time for her face to go back to normal. She seems genuinely confused about why Ethan has killed her and reaches for him as she falls; Ethan tries to catch her despite what's just happened, suggesting he still cared enough to hold her when she died but misses and Mia collapses instead.
The Sadistic Choice when forced to either cure Mia or cure Zoe. On one hand, Ethan came to the place and got wrapped up in the series of events to save his wife, and curing her is the 'good ending' path. On the other hand, Zoe was the one that helped Ethan get just the right situations to be able to both evade and fight off her own family, turning against them with hopes of escaping one day and even creating said cure herself. Unfortunately no matter what you choose, Zoe is calcified by Eveline; she appears later in the Hive Mind if you cured Mia but is rescued by Joe and Blue Umbrella after Ethan contacted the latter. If you cured Zoe, Eveline kills her shortly afterwards for betraying the family,while Mia eventually is killed by Ethan herself.
What makes this worse is the fact that Mia repeatedly pleads with Zoe to try to get her to come with, but Zoe, understandably upset, adamantly refuses and admits she was probably cursed to rot from the start with her family. Yet she still anxiously watches you leave as if not even sure with herself.
When Mia runs off after sawing off Ethan's hand, she screams "Must contain the outbreak...MUST BURN IT DOWN". And she does in again when she attacks you in the attic, where she screams "Contained. She must be contained...everyone is counting on me." It sounds like the ranting and raving of a lunatic until when you find out later about Eveline, her powers, and her hold over the Bakers and Mia and realize that Mia's screams were most likely her resolving to destroy Eveline and free herself and the Bakers. Damn.
After apparently shooting her to death in the attic, Mia's last words are a rather sad "I love you," rather than the threats you'd heard up until that point.
While a absolutely horrific fight, actually listening to Jack during his final encounter is nothing but Tearjerker material. He desperately calls out for Marguerite, explains how he just wanted to protect his family and is honestly distraught about the situation, only to occasionally return to insanity where he yells in fury at Ethan. And the real kicker? You shot all his eyes, he collapses, only to return again to attack you even more, without any mercy. But the moment Zoe tells Ethan to use the serum to permanently kill him? He stops attacking and waits. As little autonomy he had left, the moment he realized he could properly die, he embraced it and just calmly waited for you to do it.
When Ethan gets trapped, he enters the Hive Mind and meets the actual Jack, along with a depressed Zoe. Jack is a friendly old man that tells you in a calm voice that he feels sorry for what happened, that he just had wanted to help a little girl and that he and his family have never wanted to cause any harm. His last action is to carefully grab Ethans hand and beg him to kill Eveline so he and his family can finally be free.
You feel less sad for Lucas when it's revealed he was freed but kept up the illusion so he could keep his Healing Factor powers and kill people because he'd come to enjoy it. Still its possible in another scenario, Lucas could've potentially been given the mental help needed for his psychosis.
That said, it does make Jack's assertion that Lucas isn't a bad person all the more tragic. Jack either had no idea or completely denied the fact that his son is a killer at heart.
Though obviously Brainwashed and Crazy, some of the things Marguerite and Jack say are quite sad. Especially about how they just want to be a family, just want the best for everyone, oblivious and too far gone to realize what they are doing. Especially hearing Jack complain about how Ethan will be the father when he was supposed to be it and how dejected he sounds makes it quite sad. The whole time, the couple had been the designated parents in the family group, with only Mia challenging them as the "mommy", but the moment Ethan appears, both get degraded to grandparents and they don't take it well.
Although it's also scary as hell, the moments of Marguerite acting like her original sweet self at both the dining room table and when she has Clancy as a "guest" in the Bedroom DLC are pretty poignant. It's obvious in hindsight that she was originally a nice old lady, until Eveline turned her into the scowling, foul-mouthed harridan you meet in the game proper.
In Daughters DLC, we see how the infection happened. Jack finds Eveline in the bayou, and Zoe was asked to provide blankets for her. As soon as Eveline wakes up, she takes control of her parents, who are trying to fight back. Zoe was very unfortunate to see her parents becoming deranged as a result.
Just everything that happens before Zoe enters Lucas' bedroom. Marguerite is a kind and caring woman that instantly orders her family to do everything they can to help the poor little girl they found and goes to prepare some soup. Jack carried Evelyn all the way from the Bayou to the house, has some lovely banter with his wife and jokes about how he wanted to run a B&B. Lucas and Zoe are a lot calmer and friendlier as well. There is even the strong implication that they have helped people in need regularly and that they specifically might have saved some of the boat crew as they refer to the "flood victims". There is also a mention of how Marguerite had offered her own private room for Mia to stay in, showing just how much this family had their hearts at the right place. There are countless innocent victims in the Resident Evil series, but the Bakers stand out for becoming victims of the infection just because they were trying to do what was right, and one could argue that no one deserves their fate less than them.
Hell, even Lucas earns some sympathy points since it makes it clear that before Eveline, he was just a normal, albeit moody, guy trying to deal with his own life like anyone else. The absolute fear in his voice when his recently infected father drags him off to meet Eveline is enough to feel sorry for him.
And the final true scene of it with the Bakers trapped together in the Mold's Hive Mind, reliving the memory of their final morning before they found Eveline just hammers in the final nail in the coffin considering how utterly screwed they are from that moment forward. They were just like everyone else, a normal run-to-the-mill family, which ended up as victims completely by chance.
The interactions with Marguerite once Jack got Lucas are just one big Tear Jerker:
Marguerite: I'm so sorry, I don't know what is wrong with me.
And then Zoe says possibly the saddest line in the entire DLC, especially considering the Foregone Conclusion of the Bakers destiny:
Zoe: Don't worry, Mama. I'll go get help.
It can be incredibly hard to play Daughters, considering that once Marguerite has become infected, Zoe can be heard constantly sobbing and quietly calling and begging for her parents. The poor girl is understandably scared out of her mind.
More than anything else Daughters highlights what a Crapsack World the world of Resident Evil can be. No matter how good a person you are, no matter how good your intentions, there's always the chance that you'll be the poor fool who stumbles upon some B.O.W or another.
If you try to escape through the garage, you'll be intercepted by Eveline's sudden appearance, before being dragged out of the car by Jack. Both he and Marguerite begin to berate you for being rude as your father begins wailing on you. But what brings this over to Tear Jerker is that, for a second, you can see Jack hesitating before throwing the first punch.
Then, for the final dose of sadness, we have the very last DLC of the game: End of Zoe. Making the Good Ending path canon, it's revealed that Eveline calcified Zoe and left her to die in the swamp before she was herself destroyed. End of Zoe canonically starts weeks later, with Zoe still being trapped inside of her own crystallized flesh. By the DLC's climax, Zoe has been restored and reunited with her uncle Joe... but she's the last of her family. Her mom's been dead since Ethan killed her, Chris Redfield killed her brother Lucas, and Joe himself had to kill Zoe's father, Jack, after he managed to come back from the Mind Hive, but only as a deformed and horrific Molded.
The Reveal as to the true identity of "the Swamp Man" in End of Zoe. It's Jack Baker. Doesn't matter that Eveline was already killed, or that he was injected with the antigen by Ethan; the mutamycete still won't let him rest. Except now his wife's dead, his son's dead, and he's a muck-encrusted mockery of a man. He's got nothing left now. Not even his humanity.
As awesome and campy as the final fight with Jack is, you can tell Joe is deeply hurt over having to essentially kill his own brother to save his niece. At one point one of his lines is him trying to come to grips with it, calling Jack a mad dog that needs to be put down.
Eveline herself also counts, fitting the Tragic Monster trope to a tee. She was genetically engineered since she was a fetus as a living bio-weapon, and had her aging accelerated so that she could effectively pose as the ultimate subversion agent: a young girl with the ability to infect people with a special fungus that she emits and controls, allowing her to subsequently brainwash her victims. Unfortunately, in the eyes of her creators, she wasn't even human, and received no love of any kind. All she wanted was to be a normal girl with a normal family, but due to her nature as a Walking Wasteland, it's the one thing that she cannot ever have. Eventually, she escaped confinement, but that eventually robbed her of the one thing keeping her young: the medicine that keeps the accelerated aging in check. Her true form is the mysterious elderly woman who appears throughout the game.
"Why does everyone hate me?" She just seems so genuinely clueless and upset about it that it really drives home that this is all Eveline knows—she thinks she's creating the family she's always wanted, and doesn't understand that it's something horrifying.