Mission Nine (A Voice In The Dark). To elaborate, the player character finds themself in the middle of zombie-infested territory in the middle of the night. However... the scanners are down, meaning that Sam Yao can't locate you. In fact, he doesn't even know if you're alive. While you're running for your life, Sam is quietly monologuing about how he came to Abel, how you might be the fourth Runner 5 he's let die and how he was just starting to consider you a friend. And, of course, you can't contact him at all.
Mission Eleven (Alternates). Oh god... You listen in on a recording that a doctor made for her girlfriend that is, ostensibly, explaining their futile efforts towards developing a cure or vaccine for the zombie plague. But it's mostly a farewell letter. Between the the farewells, the sobs of the recipient, and the realisation that every other doctor in the building is waiting for her to finish so they can make their own before the zombies burst in and... well... let's just say choking up while running makes it really hard to keep running.
Mission Nineteen (An Unimportant Mission). Runner 10 has been bitten. While he's still alive, you have to go to his house and get a letter addressed to his daughter who cannot be located. Said letter contains a recording from her mother, who was killed right in front of Runner 10 on the front lawn. When you get the letter, he let's go and dies.
The end of Season 2. Runner 8 dies with you right beside her, unable to do anything. Runner 3 has betrayed Abel. And the cliffhanger for this Season is that Runner 5 looses some very important people to who-knows-what at the very end.
Perhaps it's just this troper being overly emotional, but it made for some serious nausea when Lem's girlfriend thought Runner Five was Lem. Particularly when Abel used it to deliberately confuse New Canton. The joy in his girlfriend's voice, plus the fact that New Canton clearly loved and respected Lem (his Runner number was retired after his death) made the whole plan sit poorly in this troper's stomach.
Eugene getting food poisoning and Jack's subsequent attempts to air by himself is listed under the Heartwarming section, and when Eugene comes back, it certainly is heartwarming. But Jack being alone and clearly at his wits end with worry, and ultimately sounding near tears as he tells Eugene to get well soon because Jack's a mess without him is absolutely gut-wrenching. You just want to reach through the soundwaves and give the poor guy a huge hug.
In a similar vein, Season 2's first sidemission has Runner 5 and 3 searching an abandoned camp, with Eugene at the desk. Despite increasing number of zombies and bad omens, he insists they keep up their job. Why? Through tears, he explains it's "because he never came back." It doesn't take much to work out who "he" is. Somewhat negated by the end of the episode.
If your morale/defense gets too low, Radio Abel segments will be tense and somewhat sad, but it comes to a head when Jack tearfully states that he doesn't think he can deal with all the "darkness and monsters". Eugene calms him down, but it's incredibly jarring to hear happy little Jack talk like that.
When starting a Tech Supply run, Janine may have a conversation with an offscreen (and probably drunk) Sam Yao. She tells him, rather exasperated, that spinning a bottle on the computer will not cause a hot woman to appear, she will not run a lightning bolt through her lab, and there is no way for a computer to bring the former Runner 5 back to life.