During the Arrival DLC mission in Mass Effect 2, Shepard learns that the Reaper invasion is imminent, and s/he needs to buy the Alliance and Council time for humanity and its allies to have a hope of surviving. To slow the Reapers, Alliance operatives have rigged an asteroid to ram a Mass Relay, destroying it and forcing the Reapers to travel for months or years to get to the next one. However, the destruction of the Mass Relay will inevitably obliterate the entire system, which contains a Batarian mining colony with a population of about 300,000. In addition, the Alliance is likely to take the heat politically, since the Batarians recently caught Alliance personnel poking around their system. With only hours to spare before the titular arrival and no other options, Shepard presses the button.
This also has the potential of occurring in several of the loyalty missions — notably Mordin and Miranda's — however, in those instances, Shepard can persuade them not to do it.
Virmire in the first game—you will have to leave either Kaiden or Ashley behind. One of the endings in the third game can count for this for the Geth and EDI.
Attempted in Devil May Cry 4. Dante's dropping into a meeting of the Order of the Sword and putting a round through the head of their leader Sanctus was meant to prevent the Big Bad from carrying out his nefarious plan. Unfortunately, that wasn't good enough, as Sanctus got better.
In Tales of Vesperia, Yuri is almost defined by this trope. Near the end of the first arc, he murders Ragou in cold blood and tosses his body into the river, because Ragou was escaping justice for horrendous crimes. Later, he repeats it with Cumore.
He also does it in the prequel movie, when Repede's father Lambert is possessed by a monster, forcing Yuri to kill him.
In the infamous "Mind of Steel" 'bad' end (#30) in Fate/stay night, having been told that Sakura, the girl he loves, will go insane through mana deprivation and kill people, Shirou decides to follow his father's footsteps by freezing his emotions in order to kill Sakura and (once he learns the true nature of the Grail) coldly win the Grail War—whatever it takes—for the sake of the greater good. As Kotomine says, now that he has turned his mind to steel, he is his father, and his success is guaranteed.
Also, killing Saber on the same route. Yes, it avoids a horrific Bad End, but at the time you have no way of knowing that, so choosing that option on your first playthrough without having read a walkthrough has many aspects of this.
In Jade Empire, towards the end of the game, you learn the secret of how the Emperor created Death's Hand and that you can use the same technique to bind him to you instead. After learning this, you're lectured on how this is the worse thing you can do to a person. You can still choose to do it and given how powerful a warrior Death's Hand is, it's pretty tempting. It really stops having the "justifiable" credentials when you then have to bind your fellow party members if you want to keep him over their objections. From the character's point of view, it's easy to see how this might look like the only way to win, but really...
In Halo 3, Sgt Johnson says Keyes must shoot him and herself to prevent themselves from being used to activate the Halos. However, it turns into a Kick the Dog when Truth intervenes and kills Keyes himself. Why Don't You Just Shoot Him? Truth that is. He didn't appear to have a shield ala Regret.
A more tragic example happened to her father in the first game. He was turned into a Flood Proto-Gravemind, and the Chief had to kill him to prevent the Flood from taking over.
In Splinter Cell: Double Agent, one of your earlier "karma choices" is to decide whether to shoot the pilot of the helicopter that the terrorist organization hijacked, as an act of loyalty to the terrorists. If Sam decides to instead hesitate and stay loyal to the government, Sam's only friend in the organization does it instead in a last-minute decision to save Sam's face.
Said choice is then taken Up to Eleven when Sam is made to choose between killing Lambert or killing Jamie; choosing the former option secures Sam's cover long enough to kill the villain and save the day with ease, whilst choosing the latter serves to risk the entire mission as of then, as well as thousands of lives just to maintain his moral code.
The above example is made even worse when Word of God revealed in Conviction that not only Sam killing Lambert is canon, but that Lambert did everything in Double Agent to protect Sam's daughter, thus only adding to the guilt of killing a friend on a whim.
In EverQuest II, if the PC wishes to become a citizen of an evil-aligned city called Freeport, they must follow a quest line where they earn the trust and love of a canine companion before being ordered to kill it.
In Fallout 3: the player comes across a computer simulation run by one Stanislaus Braun, who has been torturing its inhabitants for the past two hundred years. The action which nets the most karma? Activating a fail-safe which calls in simulated Chinese soldiers who arrive and kill everyone.
A literal example involves a glitch involving the follower Dogmeat (a dog) and the perk "Puppies!", which you get from Broken Steel. If you have the perk and Dogmeat dies, a new dog that replaces Dogmeat will show up. If you kill Dogmeat, recruit a follower, recruit the new dog, and then kill the new dog (repeating the process), you can obtain every follower in the game (normally, you are only allowed one follower and Dogmeat). You are shooting the dog for the purpose of gaining a relative army of followers.
Killing either the Overseer or Amata and the rebels in Trouble On the Homefront. If you fail the Speech challenges, this is the only option other than just walking away, or forcing an evacuation of the vault.
In Starcraft, Tassadar is forced to burn and sterilize the Terran planets that have been infested with Zerg, because it is the most effective way to kill the Zerg. After a while, Tassadar refuses to shoot any more dogs and disobeys his orders. Whether true or not, this is also Arcturus Mengsk's stated reason for everything he does.
Solar Boy Django, the protagonist of Boktai has been forced to kill off, or very nearly do so, a member of his immediate family during each of his series three games after they are enslaved by the forces of darkness. The only thing that makes it slightly easier (or even worse) for him is that they beg him to do so.
Zero had to make this decision at the end of Mega Man Zero 4. Confronted with the monster that was Dr. Weil, the latter boasts how a hero like Zero would never bring himself up to kill a human like Weil, or else he would forever be branded a Maverick. Fortunately, Zerodoesnotcare. — An unfortunate mistake Weil has made, since Zero was not created according to the Three Laws of Robotics anyway.
Throughout Metroid Prime 3: Corruption, Samus is forced to fight and kill Rundas, Ghor and Gandrayda in order to save them, in a manner of speaking, from their total Phazon corruption. Possibly doubles into a Kick the Dog moment immediately afterwards, as an incorporeal DarkSamus appears and absorbs their bodies into its own.
While you can easily be a Messianic Archetype in most of Dragon Age: Origins, when it comes to the dwarven city of Orzammar, if you attempt to give it at least a somewhat happy ending in the epilogue, you will be forced to Shoot the Dog repeatedly because apparently, in dwarven society, No Good Deed Goes Unpunished. Examples include: A dwarven girl wishes to study in the Circle of Magi. Seems innocent enough, but helping her may eventually cause the Chantry to start an Exalted March against Orzammar for harboring apostates, so you'll have to shoot her dream down. The same situation will occur in the epilogue when you help an Andrastian priest with his simple request to build a local Chantry church, so you'll have to deny him all help as well. Finally, during the main quest, you'll be forced to work with the Magnificent Bastard Bhelen who killed his eldest brother Trian and let the Dwarf Noble PC take the blame, causing him to become exiled; rather than the Reasonable Authority Figure Lord Harrowmont. Because once made king, Harrowmont will fall ill, Orzammar will close itself off from the world and fall into political chaos. But if Bhelen becomes king, he becomes a benevolent dictator who abolishes many of the restrictive dwarven policies (like the Caste System) and opens up Orzammar to the world.
Actually, the Exalted March only starts if you help the Brother trying to spread the Chantry teachings; however, the epilogue is notoriously buggy, so you might get that ending anyway.
In Metal Gear Solid 3: Snake Eater, Snake's ultimate mission is to eliminate his old mentor, The Boss, in order to avert a nuclear war. At the very end, she lays there dying, and orders him to fire the bullet that will end her life. As if that wasn't heartbreaking enough, the game forces you to pull the trigger yourself.
In Kingdom Hearts: Birth by Sleep, Master Xehanort's plan to restart the Great Keyblade War, which would devastate and reshape the universe at large, hinges around Ven, one of Master Eraqus's students, and Vanitas. When Master Eraqus realises just how close Xehanort is to achieving his goal, he's willing to kill Ventus - except Xehanort sees this coming and arranges for Terra to catch him in the act.
"This is a terrible thing we do," whispers Tzaraziko. "It will be forever remembered as our greatest crime."
"There's no other choice," says Urlach, and none are left to argue.
Summoning their magics, the shining ones circle around the child and Muud. The child screams as Muud begins sinking into the swamp, pulling the child with him. Steam rises up around them, thick and putrid, billowing in the air like cancerous clouds. Slowly, they sink deeper and deeper into the ground and away from the world above - where it will be forever silent and dark.
Poor Devlin McCormack in The Orion Conspiracy. He had to shoot a number of dogs. First he had to destroy a ship with Rowland in it. He had to explain to Meyer that the ship contained cocoons that would have hatched into xenomorphs disguised as humans. He could not afford to let such deadly creatures end up on Earth or spreading anywhere else. Also, he points out that the xenomorphs on the ship would have killed Rowland anyway. Devlin did what he had to do. However, that is nothing compared to what happens later. Ward ends up going berserk, and Devlin finds him in a corridor with Ramen and Brooks. He tried to negotiate with Ward, but Brooks jumps Ward, resulting in the deaths of Ward and Brooks, as well as heavy machinery falling on Ramen, pinning her to the floor. Not only that, but the corridor gets damaged to the point of being in danger of depressurizing shortly. Chandra appears and decides that he loves Ramen enough to stay and die with her. Devlin ends up having to seal off the doors to the corridor on both sides. Yep, four people end up dead...and Devlin feels horrible about it.
In Dark Souls, the Chosen Undead will have no choice but to kill Gwyn, who is arguably one of the most noble characters in the game, if there is to be any hope for the future.
In Planescape: Torment, this is the reason for everything the Practical Incarnation has done. He may be arrogant and manipulative, but the thing is, if he hadn't done these things, you would have never been able to regain your memories and find the Transcendent One
In the... Unfortunate Soulstorm expansion to Dawn of War the command unit for the Sisters of Battle has the quote "Thou shalt not! I shall!" Stating "I'm about to do some heinous things in the defense of the Imperium." She sounds a little too happy about it, though...
Might and Magic VI has the main characters release the Big Bad of Heroes II, leaving him free to restart his scheming to gain the throne of Enroth. There is a very pragmatic and logical reason for that: he's the only one around that knows the Ritual of the Void, and you need to learn said Ritual to keep the world from blowing up in the process of saving it. Compared to The End of the World as We Know It, Archibald Ironfist on the loose is a much better option.
In AdventureQuest Worlds, the hero is forced to kill Antiphuus during the Bloodtusk Ravine saga because Antiphuus was Chaorrupted - hoping that Sokrakiis would understand. Sokrakiis, Krellenos, and Khasaanda realized that Antiphuus' Chaorruption ended up leading to his murder and decided that there would be nothing to redeem Antiphuus' Chaorruptor. Little did the trolls know, was that Krellenos was indeed the one who Chaorrupted Antiphuus and became responsible for his murder.
King Loghaire in Arcanum is forced to banish the Black Mountain Clan and allow elves to interfere in the Dwarven justice system, an unforgivable crime against Black Mountain's honor, for the sake of preventing a war between elves and dwarves that could devastate the continent. He deeply regrets it though, and states that if given the choice a second time, he'd happily go to war with all the world for the sake of his kin's honor.
Near the end of Borderlands 2, you're required to kill Angel, who is revealed to be a Siren and also Jack's daughter, and she's kept alive by the Eridium injectors that Jack has her hooked up to so she can power the Vault Key.
The Walking Dead games has the player make painful choices of choosing to save one character over another or let one character die or not.
In 400 days, Vince has the painful choice of shooting a convicted rapists, or a con artist in the leg, to free themselves from their chains.
Played straight, averted,subverted, and all-around torn apart in Spec Ops: The Line. All of the many,many,many horrible things that happen throughout the game are done by people who claim to be doing it for the greater good or consider the acts a necessary evil. In almost every case, they're just deluding themselves.