Life's Work Ruined

Alice has been spending the the last N years of her life focusing on a single great project, putting most or all of her leisure time and free money into it. Finally, it's approaching completion...but just before she can reveal it to the world at large, an unlikely and destructive chain of Disaster Dominoes and violent intruders conspires to utterly wreck everything she has accomplished. Cue Big No. Or if you're looking to mix it up, Angrish. Specially if she had No Plans, No Prototype, No Backup.

Also a typical comedic relationship between the Mad Scientist, Wrench Wench, or Gadgeteer Genius and The Ditz or resident Cloudcuckoolander.

Compare to the relationship between the Spanner in The Works and the Chessmaster.

Anime and Manga

 * Tenchi Muyo Take Washu, add Mihoshi, cue Big No
 * For that matter Mihoshi could be a never ending occurrence of this for Kiyone.

Film

 * In How to Make an American Quilt, the protagonist's dissertation on quilting traditions gets blown away by an aggressive storm. She's pretty cheerful about it, though, because she's learned that love is more important than work. Or something.
 * Similarly, in Wonder Boys, Michael Douglas' character feels pretty good about losing the several thousand pages of his second novel, probably to indicate that it didn't measure up to his brilliant first one.
 * In the first Dennis the Menace movie, Mr. Wilson spent forty years growing a plant that only flowers once for a few seconds. So he invites the neighborhood to the flowering, but Dennis causes a distraction at the crucial instant.
 * In Twice Upon a Time, Synonamess Botch drives his head nightmare writer Scuzzbopper to attempted suicide (and a Heel Face Turn) by dismissively throwing his manuscript for a "Great A-Murkian Novel" out a window.
 * King Triton actually destroys Ariel's collection of salvaged treasure in Disney's The Little Mermaid after finding out that she was secretly in love with a human prince.

Literature

 * Amy burns Jo's manuscript in Little Women. It's clearly stated that Jo spent years (she's fifteen) of her life on this thing and that it's irretrievable as Jo destroyed the original manuscript after copying the stories to the one Amy burns.
 * A variation occurs in The Moomins, where a philatelist ruins his ability to add to his stamp collection by finishing it. After a bout of depression he becomes a botanist.
 * In the sci-fi short story The Mindworm about, the main character walks in on an artist who has just completed his ultimate masterpiece and unceremoniously smashes it. Apparently  , and he wanted a unique dish.
 * In the Knight and Rogue Series Ceciel spends her whole life experimenting to find a way to give humans magic. When she finally succeeds her test subject responds by trashing her lab, wrecking all her potions and burning all her years of notes before managing to convince her she failed anyway.

Live Action TV

 * An episode of Black Adder the Third centers on Baldrick's unwittingly destroying Dr. Samuel Johnson's life's work, the very first English dictionary. Johnson is, of course, enraged...until it turns out the manuscript that Baldrick burned was Blackadder's life's work, a novel that he'd spent over seven years writing.
 * Played with in an episode of Reno 911 where an author's novel manuscript is trapped in a burning building. He pleads with the cops to go in and save it, but they want to know if it's any good first. He describes it, but it turns out it's a derivative knockoff, and they let it burn.
 * Played for laughs in a British sketch show starring ex-Goon Michael Bentine. A guest on an interview show has spent ten years building a magnificent model of St. Paul's Cathedral out of matchsticks. Unfortunately the heat of the studio lights cause it to catch fire. The interviewer mutters, "Well, I expect we'll be seeing you again in ten years. Only this time I'd suggest taking the match heads off first."
 * In the Midsomer Murders episode "Orchis Fatalis", someone takes revenge on an orchid collector by pouring weedkiller over his priceless orchid collection. This being Midsomer, things soon escalate to murder.
 * The sketch-comedy show Almost Live regularly featured a kung-fu parody called "Mind Your Manners with Billy Quan"; the fights would often start with the same oaf thoughtlessly destroying Billy's latest painstaking masterpiece.
 * In a Wings episode, Lowell shows Joe the model blimp he's spent years creating and makes Joe promise not to play with it. Joe plays it with anyway, and it promptly gets smashed behind a door.

Myth and Legend

 * There's a legend about Saint Albertus Magnus who supposedly had built a working android, which could walk, would do household chores, and according to some could even speak. Albertus' greatest student Thomas Aquinas destroyed it (thinking it was the result of demonic possession), after which Albertus was said to have spoken: "The work of fifteen/twenty/thirty years is ruined." In Latin, of course.

Real Life

 * Subverted in Real Life with Sir Isaac Newton. In his early career he was not very good at getting himself published, he tended to just let the finished work pile up on his desk. One day his dog knocked over a candle and much of his life's work up to that point went up in flames. So he sat down and wrote it all out again. "Diamond! Thou little knowest the mischief thou hast done!".
 * Alfred Russell Wallace was a Victorian naturalist whose work parallelled Darwin's. In 1848 he began a 4-year expedition to the Amazon collecting plant and animal specimens. In 1852 he took ship back to England with his collection. Four weeks later the ship caught fire. The crew abandoned ship but most of Wallace's collection was destroyed. At least it was insured.
 * DeathOnAStick, who spent a year and a half on a single game of Nethack, spending most of that time collecting rocks, transforming them into gems, putting them into bags, and creating pet giants to hold the bags full of gems. Then he accidentally drank a cursed potion of gain level, which moves you up a dungeon level, which put him past a Point of No Return. Without his gems.

Theater

 * Hedda Gabler burns the only copy of Lavborg's manuscript, on which he'd staked his future. Unhappiness and deaths ensue. This is Ibsen, after all.

Video Games

 * A major part of the fourth game in the Ace Attorney series involves this:.
 * This is Lady Vayle's reason for revenge against Artix in Adventure Quest Worlds and Dragon Fable.

Web Comics

 * Happened to Em in Misfile. When, at the beginning, an angel misplaces two years of Emily's life that she'd spent working incredibly hard at school so she could get accepted to Harvard. She'll just have to do it all over again!
 * Sarda of 8-bit Theater has a habit of doing this to people, when he does it to himself.
 * Helen and Micah first met in Mac Hall when he accidentally jumped off a balcony and just barely missed landing on her semester project.

Western Animation

 * In a episode of The Simpsons, Bart ended up destroying George Bush Sr.'s memoirs.
 * All of those times an Ancient Egyptian is making the final few taps on the nose of the Sphinx, only to have a chase go by and make him make ONE too many taps. Poor nose!
 * Batman the Animated Series, in an episode where Mr Freeze vents his frustration by destroying peoples' life's work.
 * Avatar: The Last Airbender: "MY CABBAGES!!!"
 * Spongebob SquarePants's crashing into a truck loaded with beetroot or something similar ruins a old guys memoirs which were written with red ink

Web Original

 * Gavin's Project Orwell software in Kate Modern. When it gets stolen, he becomes bitter and delusional.