Water Source Tampering

Fear of drinking water is a classic paranoia, especially since in medieval times or earlier it could be quite difficult to come by a clean water supply (just imagine what it was like it the days before water filtration and the only river within miles had thousands of people throwing all their waste, including biological wastes, into it upstream) and thus a well could be the center of life for miles around. If anything happened to it or anyone tried to contaminate it, you'd never know until it was too late...

As such, super-villains or government conspiracies putting horrible stuff in the water has been the fodder of fictional plots for years. In other settings, the paranoia is not justified but might still be relevant to the plot.

Compare Tampering with Food and Drink, which is at least normally intended as a (deadly) prank.

Anime and Manga

 * In Birdy the Mighty, this was Seichiro Hikawa's plan for the people of Tokyo, to turn them into "retro soldiers" by tainting the city's water supply with serum starting at 4:27.
 * Ninja Scroll. A village well is poisoned to make it appear a plague is sweeping through the area—everyone flees leaving the bad guys free to carry out their plans without witnesses.

Comic Books

 * A frequent plot of The Joker is to slip Joker venom into Gotham's water supply.
 * Deconstructed in one Batman comic, where Bruce deduces the Villain of the Week won't put his hallucinogen into the water supply, because it's too easy to shut off. Instead, he plots to put it in the milk supply.
 * Supreme Power (an Alternate Company Equivalent to the DCU and especially the Justice League) was all too happy to show how terrifying this would be in the spinoff where Nighthawk (the Batman analogue) deals with an Omnicidal Maniac who has developed an always lethal poison and is trying to kill off an entire major city with it.
 * Often used as a plot point in the adventures of Lieutenant Blueberry: one or more characters finally come across a water source after a long and hellish trip through the desert... only to find out that the bad guys (or at any rate, someone who does not want to see them come out of the desert alive) have poisoned it by throwing in a dead animal, usually a horse.
 * A Captain America arc, during Cap's "The Captain" phase, had Madam Hydra/Viper putting drugs into Washington D.C.'s water supply. What did said drugs do? Turned everyone who drank the water into half-human, half-snake hybrids.

Film -- Animated

 * In Toy Story, one of Woody's quotes that play when someone pulls his string is "Somebody's poisoned the waterhole!"

Film -- Live Action

 * In Erin Brockovich, PG&E tries to cover up the fact that they were poisoning the groundwater of the town Hinkley, California with Hexavalent Chromium, which resulted in most of the town suffering from illness and cancer.
 * The plot of the old action flick Never Too Young To Die involves the hero trying to stop a bad guy played by Gene Simmons from poisoning the water supply.
 * Dr. Strangelove's General Jack D. Ripper had a paranoid belief that there is a Communist conspiracy involving water fluoridation which will lead to contamination of everyone's "precious bodily fluids."
 * In The Tuxedo, Dietrich Banning (Ritchie Coster) is the owner of a bottled water company. By infecting a swarm of water strider insects with a strain of bacteria that causes water to dehydrate rather than rehydrate the drinker and letting them loose, he plans to render all the water in the world undrinkable except his own, thus increasing its value.
 * Batman Begins had a variation. Scarecrow laced Gotham's water supply with his fear toxin for months, without anyone realizing it. The toxin had no effect in this form.
 * Signs: Bo, the little girl, would start glasses of water then find something wrong with them (such as "It has [her brother's] amoebas in it!") and stop drinking them, leaving them scattered all over the house, half-full..
 * The British government was implied to have done this in the movie version of V for Vendetta.
 * The Beast of War. the Soviet tank crew is shown emptying poison canisters into a well while attacking a village. Later on one of the mujahadeen is killed when he drinks from a poisoned well.
 * The Soviets' poisoning of every water source they come across ends up biting them in the butt later, as a Soviet helicopter crew unknowingly drinks from a pond the tank crew had poured cyanide into earlier and all die - before they can radio assistance for the stranded tank.
 * An inverted version is mentioned in Contagion. The US government wants to know if they can distribute the cure this way, but is told that it would only dilute it beyond practical effectiveness.

Literature

 * Tribesmen of Gor Fantasy Counterpart Culture to arabs/desert dwellers; an outside party causes unrest by masquerading as one of two opposing tribes and attacking the others' oases. At one point they destroy a well, which tells Tarl's best friend of the book that they aren't really tribesmen because no tribesman, no matter how evil, would destroy a well.
 * Donald J. Sobol's Secret Agents Four. A criminal organization named Cobra plans to put a drug in the city of Miami's water supply. The drug causes the victim to relive the last 24 hours, rendering them helpless.
 * "When the Past Went Away" by Robert Silverberg: Amnesia-inducing drugs are dumped in a city's water supply, leaving everybody in the city with no memory of who they are.
 * Defied by Alastor Moody in his first appearance in Harry Potter: the known paranoid drinks only from his canteen, but.
 * In The First Virtue, part of Star Trek: Stargazer, a fanatical Cordracite poisons her city's water supply in order to escalate a conflict with another race, assuming they'll be blamed.
 * In Jingo, there was a man who had poisoned the only well for twenty miles worth of desert, killing five men, seven women, thirteen children, and thirty-one camels (some of them being very valuable camels)..
 * The "next stage of testing" that leads to the climax of The Butterfly Kid is the aliens' plan to dose the New York City reservoir with the Reality Pill in liquid form.

Live Action TV

 * Played with in an episode of Star Trek: The Next Generation where Data - who has amnesia and doesn't know about his own history or Starfleet - is accused of poisoning a well in the village he's living in, but he's really trying to cure them of radiation poisoning by putting the cure in the drinking water.
 * In The X-Files episode "Anasazi", The Syndicate puts LSD into Mulder's water supply, causing erratic behavior that discredits both him and the case he is currently following. And since it wasn't just Mulder's water supply, but his entire apartment building's, it also caused at least one murder there.
 * On the Brimstone episode "Carrier", Stone has to stop a Poisonous Person before she can throw up in the local reservoir.
 * Doctor Who: In The Sensorites, the title species are being affected by a disease that the good guys later trace to a human expedition poisoning their water supply.
 * There's also the special "The Waters of Mars", in which the aliens are in the water, and use it to infect their victims.
 * The Twilight Zone TOS episode "Black Leather Jackets". A group of aliens is sent to Earth to Kill All Humans by contaminating city water reservoirs with deadly bacteria. They are in the form of teenage human males wearing the title apparel.
 * In the Highlander the Series multi-parter about the Horsemen of the Apocalypse, the Big Bad planned to contaminate water supplies with a bioweapon, For the Evulz.
 * In Power Rangers Zeo, the Machine Empire tried to contaminate all the Earth's water in order to kill off humanity while at the same time turning it into something they could swim in.

Tabletop Games

 * The Illuminati GURPS module and cardgame has the "Fiendish Flouridators" as one of it's many conspiracies.
 * Paranoia supplement Acute Paranoia, adventure "Outland-ISH". The high Programmer of ISH sector is putting a drug called ZAP! in the water supply for Infrared citizens. It tremendously increases productivity but eventually kills the drinker.
 * Magic: The Gathering has Poison the Well and Tainted Well, which can mess with your opponent's lands.
 * One short adventure for Ravenloft involved  that were poisoning a town's water supply with a toxin that induced hallucinations.

Video Games

 * Early on in Final Fantasy VI, Kefka does this to the village of Doma in one of the definitive crossings of the Moral Event Horizon in console gaming.
 * A man in the first level of Half-Life 2 tells you not to drink the bottled water in City 17 because "they put something in it to make you forget".
 * Micaiah of Fire Emblem: Radiant Dawn rejects this as a tactic to take out a well defended enemy base when it's suggested. Rather than point out the questionable ethics involved, she explains that people would see it as a questionable act, and start to question their motives, maybe turn against them.
 * Poisoning a city's water supply was a potential espionage action in Civilization II. Succeeding reduced the city's population.
 * You can do the same in Civilization IV, although instead of reducing the population directly, the city takes a huge "unhealthiness" penalty...which might just reduce the population.
 * Dragon Quest VII has Krage, whose sole source of water is a single well in the middle of town. Then it gets spiked with a poison that makes everyone believe that they're the Demon Lord. Considerable amounts of Stupid Evil antics ensue until your merry band is able to do anything about it.

Web Comics

 * Buttersafe plays this for laughs.

Web Original

 * In a Dr. Horrible's Sing-Along Blog prequel comic, the Evil League of Evil takes advantage of the city's superheroes going on vacation to try and poison the city's water supply.
 * And the song "My Eyes" has Dr. Horrible contemplating whether or not to do this. "Any dolt with half a brain. Can see that humankind has gone insane. To the point where I dont know if Ill upset the status quo. If I throw poison in the watermain."

Western Animation

 * Darkwing Duck villain The Liquidator started out as an unscrupulous bottled water magnate who was contaminating the competitor's water in order to corner the market. He fell in a vat of his own poison and became a liquid being who could control all water.
 * Spider-Man and His Amazing Friends: The Green Goblin had a plot to put goblin formula in New York City's water supply, goblinizing the whole population.
 * In The Simpsons, Homer says that Shelbyville vowed to spike Springfield's water supply in revenge for Springfield burning down their city hall, but "they don't have the guts." Three guesses what happens to Marge next.

Real Life

 * In Medieval Europe, one of the motivations for anti-Semitic violence was that Jews were accused of poisoning the wells used by Christians. This is the ultimate origin of the name of that logical fallacy.
 * Tragically (and ironically), there were a number of anti-Semitic riots and lynchings in late 12th Century Britain which ended with Jewish corpses and pieces thereof being dumped down a well, poisoning it after their deaths (most notably after the Clifford's Tower Massacre in York of 1190 AD- and the well they were dumped in supplied one of the richer Christian parts of town...)
 * In a campaign in Northern Africa during World War II, the Germans were upset to find a particular branch of Scorched Earth strategy: every oasis they came to had a sign in English stating that the oasis had been poisoned by the British army. When they complained that poisoning water constitutes a war crime, the British pointed out that there was absolutely nothing forbidding putting up false signs.