* The "Bleeding Out" mission where the Boss carts Johnny 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, who had been killed mere minutes before. Even though Gat's a badass, it was depressing listening to him believing he could still rescue the girl he loved.
* [[PlayerPunch Red Asphalt.]] Especially tragic is that the Boss, who never missed a moment to talk in the game, never said a word throughout the entire cutscene, and especially when they sat by [[spoiler: Carlos's lifeless body]], grieving for a fallen comrade. Anyone who says that the Boss was an uncaring psycho in the second game has apparently never played this mission.
* Jessica calling up ''The Mix'' to hear 'Sister Christian'. She mentions that it's "Her and Maero's song". The revenge just [[HarsherInHindsight isn't as satisfying]] after hearing that.