1:
Out of all of the Stranger missions, the happiest one has you reunite a zoophile with his favorite horse. Almost all of them are grim and depressing, and when you do the "right" thing, you often end up making people's lives worse. You give Jenny some medicine but she doesn't go with you to town, is left wondering around forever. The guy who you helped make his flying mechine only ends up dying. And Sam slowly loses his mind in his journey to California.


#2:
Birth of the Conservation Movement. You've just killed all but one of the peaceful Sasquatch, and the last one is distraught and begging you to kill him. It's up to you to decide whether or not to oblige him. All because some random crazy guy told you they ate babies. Nice one, Marston.
Least there's a easteregg in GTA 5, where the parody this scene, where it was a guy dressed up as one, and even barks for some reason.


#3:
Seth lost his family, business, and his sanity in a search for treasure.. And in the end all he got was a glass eye.


#4:
Almost everything about UNDEAD NIGHTMARE:
You were forced to kill your family friend. Your own wife and child have become ravenous, flesh-eating ghouls, as have thousands of people across the West. Once serene (well, for the most part) settlements have become fortresses against the shambling hordes, their residents dwindling in numbers. Ammo, as well as allies, are scarce. And you've got to set out into the deadly, zombie-filled land to find a cure. And along the way beloved characters are dying at every corner,


#5:
when John confronts Dutch, he tries to convince Dutch to stop fighting and just give up, but Dutch says it's not possible. When John says that mean he has to kill Dutch, Dutch tells him "when I'm gone, they'll just find another monster". And just before throwing himself to his death, in a weak and defeated voice, he says "Our time has passed, John". When you finally return home it doesn't take long for the army to betray John, just as Dutch said they would.


#6:
Nastas' abrupt, pointless death. It doesn't help he's one of the few decent characters in the game.


#7:
osing one of your horses, if you've gotten used to it. Even moreso if it's the golden horse you get specially during one of the missions. Good news is you can quickly quit the game, or more easily, just have Marston get killed, and when he respawns the horse you got attached to will be back as well.


#8:
Drew McFarlene saying "I buried more of my childrun than I raised.


#9:
Killing that corrupt asshole Edgar Ross was quite awesome wasn't it? Well it is until you realize John died in vein. Jack has become what John was. A gunslinger. However. The mission is entirely optional. The player, not Jack, ultimately chooses whether or not John's sacrifice was in vain. And considering when Jack guns down Ross, he is only left feeling empty. Realizing he was no better than Ross.


#10:
The fact John nievely thinks that he can live a peaceful life, despite his criminal history.