* "You're dying, Wilkes..."
* Sam overhears a lot of the bad guys talking to each other, joking, talking about the game's current events, even about sports. A few of them even talk about how frightened they are when Sam puts a knife under their throat, and how they do not want to die. Only rarely do they say or do anything particularly inhumane or cruel. [[PunchClockVillain They really are, for the most part guys doing a job like you or me.]] And sometimes--especially if you screw up--they have to die. Guess who has to do it?
** There's one particularly sad story in the first level, when during a thunderstorm, a Peruvian guerrilla talks to one of his buddies about how his family was killed during a thunderstorm when he was a child, supposedly by U.S. special forces. When Fisher interrogates him, the guerrilla gets all emotional.
* [[spoiler: Douglas Shetland's]] betrayal. It is obvious that Sam is trying very hard not to believe that his old friend could actually be a part of all that has been going on. He's stoic about it and tries to find alternate explanations until he simply can't deny it anymore.
* Sam watching his former commanding officer and hundreds of other sailors die during a news broadcast.
* The intro, where Sam learns his daughter was killed, and drops his iconic goggles out of the side of the Osprey into the ocean.
* [[spoiler: In the old [=PS2=]/Xbox version, Sam starts to care for Enrica Villablanca. At the end of the game, she is shot by another splinter cell and dies in Sam's arms. He strikes down the assassin in a fit of rage.]]
* Lambert's murder at the hands of the JBA. Especially cruel is the Xbox version when ''you'' are ordered to pull the trigger on your boss. Even if you take the other route and kill Jamie Washington instead, it makes no difference; the next game confirms Lambert met his end "in a dirty New York basement".
* The second to last level, where [[spoiler: 2 [=EMPs=] have just been activated in Washington D.C. (There were three, but Sam only had time to after the one that was closest to his daughter, who was alive and unharmed.) You see them exploding while Vic comments that those things are "Supposed to be clean." When other explosions happen throughout the city. That's already pretty intense, but it only gets worse. After Vic crashes the helicopter into the theater, and everyone is thankfully alright, Sam goes alone to fight his way to the White House. Along the way you see all of the people who have been affected by the [=EMPs=]. Paramedics who are desperately trying to revive a man without any power of course, A couple who are terrified of anything that may have happened to their children who eventually embrace while the man promises that everything will be alright, a car exploding which throws a person onto the ground, and a man who runs over and crouches next to them, finds out that they are dead, and steps back, mortified. I crouched next to the corpse as well and the reason I keep reffering to it as a "them" is because it was such bad shape I couldn't even tell the gender. And one of the last things you see before going back into the fight? Another car exploding next to a group of people, which is, thankfully far enough away as to not have anyone injured. However, two guys have to hold one man back, who is struggling to break free of their grip and is screaming that his wife was in that car and he needs to rescue her. The other guys are telling him that his wife is dead and if he goes in there he'll die too. His response "I DON'T CARE!" He keeps screaming and crying for a while before giving up the struggle and falling to the ground weeping. All of this made the decision to shoot Reed myself all the easier.]]
** And then there is the level where Sam [[spoiler: breaks into Third Echelon's HQ. If you have been playing the game series for some time, it really brings home the terrible series of events that have lead to this point that Sam, of all people, is breaking into this place. In a world where he questioned the loyalties of everyone he met, the rock that anchored Sam, the one thing he could rely on, was that 3E were the good guys and were doing what was right. Now they are the bad guys the world has to be saved from.]] And then, you get to [[spoiler: to Grimm's office, and find out that it was Lambert--not Reed--who had Sam believe that his daughter was dead, to protect Sam and Sarah from harm. To see Sam, a man who has become known for keeping his cool, fly into a sorrowful rage is heartbreaking.]] This, combined with [[spoiler: Lambert's death, Grimm's near-total personality change and the years lost between Sam and Sarah]] show just how profound a loss Sam has suffered, and just how much his life has irreversibly changed.
** In the co-op story mode the 2 players are agents from different factions, one being American and the other Russian, bound by a common objective. During the whole campaign, they overcome their issues and work together to complete missions that would have taken a team of regular soldiers. [[spoiler: Unfortunately in the end, they both get an order from their own HQ: their partner must die. The expression on the face of the survivor really shows how much he is affected by killing his comrade... until he gets shot in the back by Kobin; ''Blacklist'' revealed that Kestrel was the canon survivor.]]
* Although it also is heartwarming, the attention paid to [[DemotedToExtra Vic's critical condition]] throughout the game is heartrending, as it is difficult to see him making a full recovery.
* Brigg's getting shot by Sadiq in a callback to Wilke's death but subverted.
* Having to execute [[spoiler: the Secretary of Defense]]. The guy's already been broken by torture and is about to give Sadiq the information he wants leaving Briggs with no choice but to kill him before he can complete the file transfer.