Metroid Prime 3: Corruption took a stab at it. Early in the game, you are introduced to fellow bounty hunters Rundas, Ghor, and Gandrayda. Upon completion of the Norion mission (and infection by Dark Samus), all three are sent to different systems. Who thought that being forced to fight the corrupted hunters, and then watch Dark Samus assimilate them when it was all said and done, was unbelievably tragic.
It's even worse with Rundas, considering he saved your life after you beat Ridley. Ghor isn't much better, though you'd have to read his backstory in one of his Logbook entries; he's such a good person that you can't help feeling terrible for having to put him down.
Made even worse by the fact that at the end Samus reflects on meeting, and then eventually killing the hunters, and you get to see all their deaths one after the other (especially Rundas'). Tragic.
And of course, it's implied in cutscenes that Samus is very angry at the one responsible (Dark Samus) and the player is probably feeling the same. Naturally, the ensuing Roaring Rampage of Revenge that ends with Dark Samus erased from existence along with all the Phazon in the universe is probably very satisfying for the player.
Call of Duty 4 employs a variation: at the start of the game, in accordance with Call Of Duty tradition, the player controls two characters, a British SAS operator and an American Marine. During the Marine's segments, he and his commanding officers are established as sympathetic and heroic characters, even going so far as to risk their lives to stop and rescue a downed - and similarly sympathetic - helicopter pilot in a city where a nuclear warhead has just been discovered. The Dragon ends up detonating the warhead before either character can escape, allowing the player to experience the Marine's slow, agonizing death from radiation poisoning in first person.
At the end of the game, after escaping the Russian missile base and evading the Ultranationalist pursuers, the bridge gets blown up, and you get to watch as Griggs gets ventilated while trying to help you to your feet and Zakhaev executes Gaz. The wounded Captain Price slides you his sidearm, which you use to kill Zakhaev. When the cavalry arrives, you then get to watch as a medic tries to resuscitate Captain Price while you're loaded onto the helicopter. MacTavish (the "you" in this POV) does survive for the sequel but dies in Modern Warfare 3 (more on that later).
Modern Warfare 2 was even worse. If the death of Private Allen wasn't bad enough, the scene where Roach and Ghost are shot by Sheperd and set on fire (In Roach's case, WHILE STILL ALIVE) is like being kicked in the balls.
Shepherd: "Do you have the DSM?"
Ghost: "Yes sir. Got it right here."
Shepherd: "Good. That's one less loose end." (Gunshot. Gunshot.)
Ghost's anguished scream makes it even worse.
Modern Warfare 3: The death of Soap. It's slow and agonizing.
Near the end of the game, members of Delta Company, Sandman, Grinch, and Truck, sacrifice themselves in a Siberian Diamond mine so Price and Yuri can escape. In the final level, Yuri (who you're not playing anymore) is killed by Makarov.
Speaking of Call of Duty, Black Ops gives us the death of Dimitri Petrenko. The mighty hero of Russia, who stormed Berlin and took it from the Nazi hands, is poisoned by Nova-6 and dies with his face melting into blood, quick and yet painful. Though people who haven't played World At War won't get why this is a Player Punch, those of us who have pretty much agree with what Reznov has to say about the situation.
Reznov: "Dragovich... Kravtchenko... Steiner... All must die."
The end of Half-Life 2: Episode 2, when Combine Advisors kill Eli Vance in front of his incapacitated daughter and the player. It'll be hard to create better marketing for Episode 3 than the desire for vengeance created by that scene.
Listen to Merle Dandridge getting choked up in the commentary track for an amplified Player Punch.
The beginning is almost as bad - at first, when you're trapped under the trailer/building and are forced to watch Alyx get impaled by the hunter.
In The Darkness video game, Jenny's death was a brutal player punch that not only made players want to kill Paulie Franchetti, but also got him to see the titular Darkness as not just a case of Cursed with Awesome, but cursed with plain old curse. "Awww, what did they do to Jenny?" Bastard!
The most punch-esque part about that scene? The fact you're right there, and the Darkness is physically restraining you.
And all of that hatred towards Paulie Franchetti leads to a big letdown. In the comic, Paulie's death is horrid. Expectations of ripping the fat bastard apart with your darkness powers are dashed when he holes up in the top of a lighthouse and you have to simply shoot him. In a way, not even getting to make him really pay for Jenny's death is another Player Punch.
Halo 3 does this twice; the first is when Truth kills Commander Keyes, and later when Spark fatally wounds Johnson.
A non-death-related version of this takes place in the level "Cortana," where Cortana, her voice audibly shaking from the brutal trauma she suffered at the Gravemind's hands, begs you to blow up High Charity. It isn't necessary from a storyline perspective, but letting Cortana get payback after what she's gone through feels damn good. "Hell Hath No Fury" indeed.
Halo: Reach. Where to begin? Was it Jorge's death? Or was it Kat's? Perhaps it was Carter or Emile's? Or Six's? What about that level where you attempt to escort civilian transports safely, only to see each one explode in front of you? Or possibly watching your entire fleet being blown to bits as you watch?
What about ODST and Reach? They both have something in common: you have to kill the innocent (and freakishly adorable) Engineers. If you've read the novels you already know that they're harmless and only interested in repairing things (one even saves Master Chief when he's in a tight situation), and if you haven't ODST reveals it anyway. And you have to slaughter them.
For a game that's Denser And Wackier than its predecessor, Borderlands 2 rolls with some pretty rough punches, particularly in the Chapter "Where Angels Dare Not Tread". It is here where you find out that Angel, the artificial intelligence throughout this and the original game, is an actual person, as well as a Siren (of which only six exist at any given time) and the daughter of Big Bad Handsome Jack. After helping her thwart Jack by killing her so she couldn't power the Vault Key that would give Jack power to completely rule over Pandora, when the dust seems to settle, Jack appears out of nowhere to kill Roland (one of the original Vault Hunters) and kidnap Lilith to continue charging the Key.
BioShock manages this by making the Big Bad Andrew Ryan blow up the wife and kid of Atlas, the one character who had extended a helping hand to the player. Later on, this trope really does make things personal because that whole wife and kid thing was just a lie by the real Big Bad, Frank Fontaine, who was just using you from the start!
Then you meet Andrew Ryan and he reveals your true identity, and the realization that both the player character and the player have been mindless pawns for the entire game. What's worse is, even if you replay the game knowing all this... you still can't do anything about it.
On a slightly more generic note, it can be utterly crushing the first time you bring down a Big Daddy and have to watch as the Little Sister it was protecting sits at its side, shaking its massive, lifeless face-dome and begging it to Please Wake Up. Even if you're doing the noble thing of not harvesting the life out of the mistreated little moppets, it really kicks you in the teeth the first time you see it.
Possibly the worst is the very first time you do such a thing, because what is playing in the background? None other than Lady Day singing ''God Bless the Child''
Players take on the role of a Big Daddy for an Escort Mission. Protecting the Little Sisters throughout is almost impossible, and though there is no gameplay consequence, watching one die, and the subsequent guilt trip from Dr. Tenenbaum, delivers a fresh new Punch.
BioShock 2 had another particularly cruel one: in Fontaine Futuristics there's a Big Daddy that looks and acts like any other one you encountered thus far, and probably the last you'll deal with. Of course, if you're playing the game normally, you kill him. Then you go loot his corpse...and you discover that said Big Daddy is Mark Meltzer, captured by Lamb and faced with the choice of being executed or becoming a Big Daddy and protecting his daughter turned Little Sister. This is particularly painful for people who followed the "Something In The Sea" ARG, which detailed Meltzer's efforts to find Rapture and rescue his kidnapped daughter. And then, in the final level, she does the same thing with Augustus Sinclair.
If you Harvest a little sister, the subsequent ones respond to Delta with fear, saying things like "Oh, no! Daddy's home! I-I've been good. Promise" and "You're never gonna hurt me, right?"
Bioshock 2 can even end with a player punch if you decide to kill Grace Holloway, Stanley Poole, and Gilbert Alexander and harvest Little Sisters. Turns out Eleanor was watching you do all this and, since her personality is being shaped by your actions, she becomes a ruthless monster, just like daddy.
Clive Barker's Jericho has Simone Cole and Xavier Jones, who are the "smart ones" of the group. Cole is given a decent degree of characterisation over the course of the game, and, while little is revealed about Jones, he seems to have a warm, likeable personality. So, imagine utter horror when, close to the end of the game, they are mercilessly blown into bloody chunks by the main villain in a flurry of gore, and not even the squad's two healers are able to bring them back from the dead. OUCH.
SHOGO: M.A.D. sees the likeable plump mechanic, who saved your posterior before, get killed for his troubles. Oh you are going down, evil bad guy...
To put it in the words of the protagonist:
Sanjuro: Ryo is going to die, and it's going to be bloody.
In Prey, your abducted girlfriend gets attached to the body of a cybernetic spider-thing and the player is forced to kill her. She is completely conscious and aware of the happenings, but can't do a thing. This is a turning point of the story - until then, the PC only wanted to escape from the spaceship, now he wants to destroy, or to be more accurate, kill it.
F.E.A.R. featured Alice Wade, the only genuinely good character to be involved with the evil corporation, who had prior to the game events been trying to dig up exactly what happened in the secret weapons project. You rescue her, only to have her run to try and help her dad out. Instead, you find her dead and partly eaten by the big bad, who is also her nephew.
F.E.A.R: Extraction Point (the expansion pack) has the player fight with the team's Demolition Expert, Holiday, for several missions. Only for him to be brutally ripped to shreds before the player's own eyes.
Perseus Mandate has Lieutenant Chen, who you spend most of a couple of levels with, just listening to him making small talk. Then one of the monsters drags him halfway into the floor and rips him apart, while he's conscious, struggling, and screaming for help. You can even grab his arm and try to pull him out, but all that happens is his arm rips off.
Latest Left 4 Dead 2 downloadable content reveals Bill from the first game is dead. The characters only care about the weapon he's holding.
The punch cranks up to 11 with the release of The Sacrifice DLC, where you get to play out how Bill dies (or anyone else in your group but in canon, Bill is the one who dies). He sacrifices his life to restart the generator so the bridge can be fully raised, bringing the other survivors to safety away from the horde and multiple Tanks.
Killzone 2 does it as well. Somewhere halfway through, Garza dies. He was the awesome one who you mostly teamed up with and you watched him die from a stupid bullet wound. Thank the creator there are still plenty of Helghast left to turn into bullet receptacles.
Not to mention that the end of the game implies that killing the leader of the Helghast will do no good, which makes just about everything you did in the game up to that point entirely pointless.
Which is turns into a bit of a jumping-off point for Rico, since your orders were to detain the Helghast emperor alive, and that Rico executing him is foreshadowed to be be what the conflict in Killzone 3 is over. Of course, you are kind of expecting this from Rico at this point, but it still doesn't help anything.
Crysis 2 The player wandering through the tunnels under Grand Central and sees the sick people there, including some guy pleading to see his sick wife. The player escapes Grand Central Station when it comes under attack, with a building is about to fall on it, and the jeep is waved down by the same man, whose wife is trapped under some wreckage. The camera view keeps alternating from the people that are trying to get the woman out (as she pleads for them to hurry) to the ever-approaching building, and ultimately the jeep you're riding in is forced to leave as the building hits, crushing them all in full view of you.
Another game promising to heavily feature this is Homefront, an FPS based on an invasion of the US by a revitalized and superpower level North Korea: the developers wanted the game to show the effects of war on civilian population. Thus, the game begins with you getting dragged by NK soldiers into a prison bus going off to who knows where and helplessly witnessing through the window soldiers executing a civilian couple in cold blood in front of their own child with the mother's last words being desperately screaming at the child not to look.
In Singularity The death of Devlin at the end of the first mission was a bit of a shock. Any Genre Savvy person knew that it was coming, but unlike a lot of throwaway allies in FPS games, Devlin was a fairly likable guy and actually managed to be pretty useful. Then Demichev shoots him in the face without a second thought.
SWAT 4: "The Children of Tarrone" A doomsday cult plans to blow up their on compound, taking a large chunk of urban housing with them. At some point during the mission you discover they the cult members have killed all of their own children as part of their suicide ritual. This can lead to executing all of the people you just arrested, the first time you discover it.
"Comrades"; Dima's squadmate Vladimir is mortally wounded by an RPG, and must be left behind. It doesn't truly become tragic till the end, though, when they find that the nuke they'd been tracking was never there to begin with, and the real bomb goes off seconds later, rendering Vladimir's sacrifice meaningless.
"See No Evil"; after two missions of following Jono Miller and learning of his desire to return home to his son, he gets captured by PLR forces, and is brutally executed by Solomon in a live broadcast.
"Rock and a Hard Place"; pushed into a battle they were unprepared for by their inept captain, Misfit 1-3 barely manages to fight off a Russian airstrike, only to find that Campo and Matkovic were killed in the crossfire.
"The Great Destroyer"; Blackburn's only remaining friend, Montes, manages to help him escape from captivity and confront Solomon, only to be shot dead by him before Black could finish the job.
Metro 2033 gives the player a solid one in the endgame. If you're playing on Ranger difficulties (which is hinted to be the canon difficulty), your air will likely be running incredibly low by the time you reach the top of the tower. Fridge Horror ensues when you realize that no matter what choice you made at the end, your character is essentially doomed to suffocate with only about 3 minutes of air remaining, as you couldn't possibly make it back under ground in the time you have left. Likely to be hand waved in Metro: Last Light, though.
Dead Island and it's expansion do this with their trailers. In Riptide we see a couple on a romantic yacht cruise where they are hugging, holding hands, crying...gas tanks placed on the stove? Turns out they had become shipwrecked and a crowd of zombies are closing in. As they look lovingly at each other they both start a lighter, killing themselves rather than be turned. Grim, but if you somehow missed the viral first trailer then in comparison the force this hits would make Mike Tyson envious.