In a formal Tragedy, there is a specific scene where the Tragic Hero is given a clear choice, and they choose wrongly. Often this wrong choice can be blamed on the hero's Fatal Flaw, but sometimes they just get screwed over by fate. (Classic Greek theater liked to give their tragic heroes dilemmas with no correct choice.)
This moment may not be obvious at the time, but looking back, it becomes clear that this moment was crucial to the hero's tragic downfall. The results of this bad choice lead inexorably towards the hero's catastrophic end—had the hero chosen correctly at this point, the catastrophe could have been averted.
The literary term for this is hamartia, a Greek term from Aristotle's Poetics (and an admittedly vaguely-defined one—it can also be interpreted as a Fatal Flaw). Which also means this device is Older Than Feudalism.
Structurally, this moment is the Crisis of the story (or just this character's story arc), and everything afterwards is Denouement.
As the Tragic Mistake is one of the most crucial moments in the story expect a lot of spoilers below.
- In Code Geass, Lelouch's Tragic Mistake would undoubtedly be when he accidentally Geassed Euphemia into massacring the gathered Japanese. He had intended to embrace her Special Administrative Zone wholeheartedly, but he didn't know until it was too late that he was suffering from a sudden onset of Power Incontinence: an offhand comment became an irrevocable command, and he was forced to kill his beloved sister, tarnish her name, and destroy a fleeting chance at peaceful resolution.
- Star Wars: Revenge of the Sith. Anakin had made many mistakes prior to this point, but what pushed him irrevocably over to the Dark Side was his decision to save Palpatine, leading directly to Mace Windu's death and leaving him no chance to go back.
- Scarface: Tony makes many mistakes, but the point of no return was when he killed Sosa's hitman to prevent the unnecessary murder of innocents, antagonizing the only person who could have helped him out of his own mess.
- Another point of no return was when he killed his best friend and right hand man thinking that he betrayed him. The friend was actually about to tell him that he is in love with Tony's sister and they just got married. This leaves him completely alone with no allies left and completely demoralized. The old Tony might have been able to find a way to survive the consequences of killing Sosa's hitman but after that point he simply did not care anymore.
- There Will Be Blood has a moment in the middle where Daniel Plainview is about to enjoy a meal with his son H.W. in a restaurant. They've been apart while H.W. was at a school for the deaf, and Daniel has been trying to reform because his lifestyle indirectly led to H.W.'s deafness. It looks like he's about to turn over a new leaf and create a healthy relationship with his adopted son, when in walks a businessman from earlier in the movie, who had turned down Daniel's offer. His Pride bubbles up, he makes a scene and he reverts to his highly confrontational self. From here, It Got Worse.
- Neil McCauley in Heat would have gotten away from the aftermath of the heist he pulled scot free had he just stuck to his regimented game plan and not decided to make an impulsive detour to settle scores with the man who betrayed him instead of going straight to the airport with the woman he loves. Doing this alerts his Worthy Adversary Lt. Vincent Hanna that he's still in town and where he is, he gets cornered and eventually shot dead.
- Another case in the movie is the paroled criminal whom McCauley recruits for the final heist. He had no involved in any of the crimes so far and could have easily said no to the offer and walked away. Instead he makes an impulsive decision and ends up killed by the cops.
- Things Fall Apart: Okonkwo raises the political prisoner Ikemafuna like his own son for three years, and then the village elders decree that the boy must be executed. The oldest man in the village warns Okonkwo to have nothing to do with the killing, or else it would be an offense to the gods, as if he had killed his own child. Okonkwo disobeys, and help to kill the boy so as not to appear weak before the other men.
- The fallout: The gods send bad luck Okonkwo's way, culminating in an accidental killing that forces him to go into exile for seven years. In that time, white colonists move into the Ibo village; without Okonkwo's leadership the Ibo get taken advantage of and lose their will to fight for themselves. Okonkwo, upon returning, tries and fails to organize a resistance, and hangs himself.
- A Song of Ice and Fire's characters tend to fall victim to the inevitable hubris of their Tragic Flaws, but a couple of them can pin their failure to definitive points of no return. Eddard turning down the help of Renly and Littlefinger and warning Cersei that he knew her secret, expecting her to flee to safety, resulted in her killing the king and installing her son, who has him executed for treason. Robb's decision to marry Jeyne Westerling sets off the events leading to the Red Wedding.
- In The Children of Hurin, it was Turin fleeing Doriath and refusing to return that led to all his misfortune and eventual death.
- In Supernatural, efforts to save the world at any cost seem to backfire whenever a character decides that they're The Only One who can do so instead of relying on friends.
- In season four, Dean demands Sam dissolve his alliance with the demon Ruby and giving up drinking demon blood to gain the power to defeat Lilith, as per the angels' requests/warnings, or walk out and "not be brothers anymore". Since Dean calls him a monster and "closes that door" on him just like their father did, and Sam believes what he's doing is the only way to prevent the Apocalypse, it's more believable how Ruby and the angels deceive Sam. He becomes Lilith's/Ruby's Unwitting Pawn and, in his efforts to stop the Apocalypse, unintentionally busts Lucifer out of Hell to start The End of the World as We Know It.
- In season six, Castiel chooses not to seek Dean's help in fighting the civil war in Heaven, and instead makes a Deal with the Devil, breaks Sam's mind, and kills his angel friends so he can gain the power of Purgatory's souls to win the war to prevent the Apocalypse from being restarted. Then he declares himself the new god. In season seven, things go downhill from there as Castiel's actions unleash unkillable monsters on the world.
- Hamlet: The prince learns that Claudius was indeed guilty of murdering his father, and catches Claudius unawares while praying. Instead of avenging his father right there, Hamlet decides that it's not good enough—he wants Claudius to die with unpaid sin on his soul, so killing him in the act of confessing won't do. Hamlet resolves to kill Claudius later. The fallout: Hamlet does attempt to kill Claudius later, during his confrontation with his mother, only he kills Polonius instead by mistake. His death drives Ophelia to madness and death, and angers Laertes enough to challenge Hamlet to a duel—the duel that results in the death of nearly every named character.
- For extra irony, Claudius notes, just after we see Hamlet leave, that his praying is nothing more than lip service because he can't put his heart into it.
- Macbeth: The title character's point of no return came when he killed King Duncan.
- Oedipus the King straddles the line between being undone by a fatal flaw and being screwed over by fate. The crime for which he was punished was that he killed his father and married his mother—but due to circumstances completely beyond his control, Oedipus never knew that they were related to him. On the other hand, you could say that this would not have happened if Oedipus had not, in his pride, quarreled with and killed another chariot driver on the road—a chariot driver who ultimately turned out to be Oedipus' father.
- Another spin on Oedipus' fatal mistake is not the initial killing—that's just bad luck. The mistake is that years later he keeps asking questions until he finds out the truth, leading to the suicide of his mother/wife and his on anquished self-blinding.
- In Romeo and Juliet, Romeo's "point of no return" was his killing of Tybalt in vengeance for Mercutio, leading to his banishment from Verona. Granted, Tybalt was a supreme Jerkass who probably deserved it, but everything still goes to hell for both lovers because of it.
- Sweeney Todd: The Demon Barber of Fleet Street: Though it's arguable that Sweeney Todd's hesitation in his first attempt to kill Judge Turpin, a la Hamlet, was the point of no return for him, his real point of no return was when he killed the Beggar Woman, who he did not know was actually his wife, because he had no time left before the Judge showed up for the second and last time.
- In Jules Massenet's opera Manon, the downfall of the eponymous protagonist begins when she chooses to stay with the rich codger de Brétigny, instead of going to the convent as planned, or taking the hand of the penniless young hunk des Grieux. Other versions of the Manon story are similar.
- Medea: Though Medea is the protagonist, Jason is the borderline Fallen Hero, victim of his own pride and machismo.
- Suikoden 2: Jowy had the heroes in an Ambush and could've easily killed them off - except Shu threw Pilika at him. He lets the group go, deciding he couldn't risk harming her. His strategist remarks he blew his chance. The fallout: The War continues on, turning in the hero's favor, and Jowy is ousted from the throne. (What happens depends on the player's choice.)
- This is what pushes Redcloak into Anti-Villain (or flat-out villain) territory in The Order of the Stick prequel book Start of Darkness. His brother Right-Eye decides that nothing they accomplish working with Xykon is worth his casual slaughter of their own troops, and acquires a weapon that can destroy Xykon despite him being a lich. Redcloak, on the other hand, thinks that it will all have been meaningless if he backs out, and kills Right-Eye. To make matters worse, Xykon reveals that he already knew about Right-Eye's plan and had taken steps to protect himself, but wanted to see what Redcloak would do.