- "Bleeding Out", which features Aisha getting decapitated by Jyunichi right in front of Johnny Gat and the Boss, and then the Boss carting Gat, who'd been impaled by Jyunichi, to the hospital. The entire way there, you can hear Gat have a near-death dream where he's attempting to rescue Aisha. It is very depressing listening to him believing he could still rescue the girl he loved.
- During one of the Sons of Samedi missions, Mr. Sunshine sics the junkies who usually buy from him to get the Loa Dust the Saints have, saying that they get to keep everything they steal. So, cue you having to fight off junkies while moving a truckload of Loa Dust. At the end of the mission, two of them manage to get each a box of the stuff and try to run for it, only for the boss to kill one and shoot the other on the leg. Then he demands the junkie to tell him who sent him, with him refusing because "You're still going to kill me anyway". The boss replies that he is in no rush and proceeds to step on the wounded leg. Finally the poor guy breaks and the boss lets him keep the box of stolen drug. The final shot is of the poor pathetic junkie holding unto that box.
- "Red Asphalt". Especially tragic is that the Boss, normally a Talkative Loon, never says a word throughout the entire cutscene, and especially when they sat by Carlos's lifeless body, grieving for a fallen comrade. Anyone who says that the Boss is an uncaring psycho in the second game has apparently never played this mission.
- Jessica calling up The Mix 107.77 to hear "Sister Christian". She mentions that it's "me and Maero's song", and that its their anniversary soon. The revenge just isn't as satisfying after hearing that. Even worse is when DJ Darius says "I bet you two will make it". They don't.
- The secret last mission, where you and Julius fight together one last time against Ultor. It's just like old times, you and him shooting it up in his custom Eiswolf. You think everything is forgiven, even Julius thinks so, calling you 'playa' like a friend one more time before The Boss shoots him. He calls you a sociopath, and tells you—more or less—that the path you are walking down will doom you. Then you kill him. The worst part of it all is that you realize he's right. In a game that is all about goofy escapist fun, the seriousness of this scene can be a shock.
- The wiretaps that trigger this mission are also quite upsetting. During the second wiretap, Troy, despite being an undercover cop, was completely willing to clear Julius' name if he managed to convince Johnny Gat and the Playa to drop their flags. The final wiretap, which takes place right after Hughes' bomb explodes, Troy is noticeably upset and chews out Julius.Troy: (angered) What the fuck was that!?Julius: It was the only way.Troy: I said talk, not set off a goddamn bomb!Julius: Relax, Troy, it's over. Don't try and find me.
- The wiretaps that trigger this mission are also quite upsetting. During the second wiretap, Troy, despite being an undercover cop, was completely willing to clear Julius' name if he managed to convince Johnny Gat and the Playa to drop their flags. The final wiretap, which takes place right after Hughes' bomb explodes, Troy is noticeably upset and chews out Julius.
- Aisha's funeral. Gat's Tranquil Fury beating is awesome but the final line where he slightly raises his voice shows why he won't show mercy now, even though he was willing to let Shogo walk away to die another day before that.Gat: You couldn't even let her have a burial you fucking piece of shit!
- It should also be noted that this is the second only time in the game The Boss doesn't speak a word.
Tear Jerker / Saints Row 2