Experiments requiring a human test subject shall be performed on kidnapped anti-social bums who live alone in large cities, not someone who people will notice the disappearance of, like a female student at the local high school.
In Hard Target the Big Bad is the head of a hunting business which allows rich men to hunt homeless or down-on-their-luck war veterans. Homeless or down-on-their-luck so no one cares, war veterans to make it interesting.
In Surviving The Game the Big Bad is the head of a hunting business which allows rich men to hunt homeless or down-on-their-luck war veterans. Homeless or down-on-their-luck so no one cares, war veterans to make it interesting. No, this is not a redundant entry.
Classic 1980s B-movie C.H.U.D. plays this straight and also inverts it. Several homeless people start turning up missing, but only two workers at a soup kitchen seem to notice or care about this. Later, it's revealed that they're the victims of other homeless people who have been mutated into killer monsters due to exposure to illegally dumped toxic waste and have begun to munch on people who aren't deemed disposable by the powers that be. Along with being a horror movie, the film also functions as a Take That against Reagan-era policies toward the homeless and mentally ill.
In The Blob, the titular monster's first victim is a vagrant whose name we never learn and who exists merely to show the destructive effects of the blob.
In Rat Race, when a heart meant for an emergency transplantation gets damaged, the character responsible for delivering it suggests looking for a 'drifter', killing him and cutting his heart out as a replacement. At which point the driver starts asking questions about the character's background.
In Die Another Day, a doctor provides Magic Plastic Surgery for his patients by re-writing their DNA. This process requires DNA from other people; the doctor mentions that most of this is harvested from vagrants and other people who won't be missed.
The villains of the novel Rainbow Six use homeless people as test subjects for their plan. The book spends quite some time following them as they have no clue what's going on.
In the sci-fi book Parable of the Talents, the Christian America cult started out with putting vagrants in their concentration camps because nobody would notice or care.
CS Lewis' Out of the Silent Planet opens with mad scientist Dr. Weston debating whether to kidnap a homeless retarded boy or his best friend from college for his rocket expedition.
Michael Stackpole's Wolf & Raven short story "Fair Game", set in the world of the ShadowrunTabletop Game. The Pacific Northwest Hunting Club is made up of wealthy people who hunt humans once per month. They choose their prey from among the SINless of Seattle, who are not part of the system and whose deaths are not even investigated.
Whitley Strieber's novel Wolfen. The title monsters have the New York ghettos as their hunting grounds. They kill and eat the abandoned of humanity (homeless, drug abusers, outcasts), those that will not be missed.
In NightWatch Final Watch when a renegade vampire needs to murder and drain five dozen people to ascend into a High Vampire, he goes after migrant workers, knowing that, since they are mostly not registered, nobody is going to miss them.
Subverted by Sherlock Holmes. His network of homeless people sees basically everything that goes on in London, and all he has to do to get information is to provide a hot meal.
Grimm featured an episode with this part of the villain's plans.
On an episode of Barney Miller, a homeless man comes to the station to report that several other homeless people have mysteriously disappeared. Harris goes undercover as a homeless person and discovers they had all been kidnapped and forced to work as slave labor on a farm in North Carolina.
In the old series, The War Machines featured a vagrant who had slept in an empty building the villains had taken over. They kill him.
The most notorious Doctor Who example is the incomprehensible Pigbin Josh from "The Claws of Axos".
Resurrection of the Daleks begins with a homeless guy witnessing some escaping test subjects being gunned down by the Daleks' human minions, before he himself is shot as well.
In the new Doctor Who the homeless were rounded up to become the new Cyberman army in "The Age of Steel".
We don't learn if this actually gets noticed or not, as the first thing the first batch of Cybermen do is start rounding up everyone else to convert.
Later subverted in the final scene of "Day of the Moon," when a Creepy Child approaches a homeless man and says, "I'm dying. But I can fix that. It's easy, really... see?" She holds out her hands, and we wait for her to suck his life out in some gruesome fashion... but instead she begins to glow, and then erupts with the golden energy of a Time Lord regenerating.
In Fringe, a WWII Nazi tests out his ultimate weapon near a homeless person to see if he dies.
In the pilot episode of RoboCop: The Series the bad guys were harvesting homeless people for their brains, and only got caught when they moved from homeless to an OCP company secretary.
At least one murder on Law & Order: Criminal Intent was hoping that the police wouldn't look too hard at a bunch of dead homeless people turning up. Big mistake.
In The Cape, several lived in the train yard where Vince "died." They're being arrested on trumped up charges rather than killed though.
In The Invisible Man, the Doctor who helps Hobbes has been harvesting brain cells from the homeless.
Jimmy McNulty from The Wire both exploits and inverts this trope when he fabricates a fraudulent serial-killer case around the corpses of vagrants, in order to attract media and political attention and divert funds to real police work. Exploited, because he only gets away with it by doctoring files on deaths nobody otherwise cares about, and inverted because "drawing attention to the vulnerability of the homeless" is the reason given for openly courting the media (although he's fully aware that what really gets it into the headlines is the juicy "serial killer" angle). He even "abducts" one live vagrant (putting him up in an out-of-the-way dosshouse) to add a sense of urgency to the case.
A Mad Scientist in Lois and Clark states she always uses people who won't be missed for her experiments... and is very distressed to learn the latest subject was undercover.
One episode of The Pretender featured a research doctor who was testing his resuscitation drugs on the homeless— which meant stopping their hearts.
In the Tales from the Crypt episode "Mournin' Mess" a secret society of ghouls start a funeral service for homeless people (that they kill) so they can eat the corpses without the risk of being caught gravedigging. Slightly subverted since it's implied that the ghouls have to bribe city officials to keep the police from investigating the violent murders too closely.
Some of the city officials were members of the (G)rateful (H)omeless (O)utcast & (U)nwanted (L)ayaway (S)ociety.
In one episode of It's Always Sunny in Philadelphia, Dee and Charlie think they've become addicted to eating human flesh. Since they can't bring themselves to eating people who are already dead, despite finding a morgue attendant willing to let them bring a hotplate into the morgue, they convince a homeless kid to come up to their apartment and start rubbing him with spices. He manages to get away before they can bring themselves to go through with it.
The Gang will often call on the same homeless man, Rickety Cricket, time and time again for various unspeakable jobs; selling drugs, wrestling a psychopath, kneecapping a dancer. Once he was even hunted.
The UnSub in the Criminal Minds episode Legacy kidnaps homeless people, prostitutes, drug users etc. and kills them. He's only caught because a detective whose OCD forces him to catalogue everyone he comes into contact with on the streets notices that 63 of them have disappeared without a trace.
Cthulhu Companion adventure "The Rescue". A group of werewolves deliberately targets derelicts; by victimizing those without friends or money, they ensure that the police are not unduly concerned.
Glozel Est Authentique! by T.O.M.E. The Shub-Niggurath cultists in Glozel perform Human Sacrifices using drifters and other strangers not likely to be missed.
Shadows of Yog-Sothoth adventure "The Hermetic Order of the Silver Twilight". Carl Stanford has an enchanted cane that drains the Power from those it touches and stores them as Magic Points in the cane. He has his minions bring derelicts to him so he can drain them until they die.
The Asylum and Other Tales adventure "The Asylum". The worship of the Great Old One called Arwassa requires a human sacrifice each month. The cultist worshippers sometimes send out kidnappers into neighboring counties to capture derelicts and vagrants for this purpose.
Masks of Nyarlathotep
Chapter 3 "Egypt". After Nitocris is resurrected, she creates an international organization to infiltrate countries around the world. Its task is to create a racial, religious or economic underclass in each country that can provide Human Sacrifice victims for Cthulhu Mythos cult activities.
Chapter 5 "Shanghai". The Order of the Bloated Woman chooses its victims from among those who are poor and have no friends.
In the supplement Volo's Guide to Waterdeep, a mimic monster took the shape of a statue in a city square, killing and eating drunks on dark nights for two years before an investigation was launched and it was discovered. A nearby sewer was found to be filled to a depth of 60 feet with human bones.
Supplement RR3 Van Richten's Guide to Vampires says that vampires often kill poor people whose loss won't be noticed.
Module A Darkness Gathering. A Thieves Guild leader (who is under illithid control) orders her underlings to kidnap vagabonds, beggars and visitors to the city. She has their heads cut off and given to the illithids so they can eat the victims' brains.
Module A4 In the Dungeons of the Slave Lords. The lacedons (aquatic ghouls) who live offshore from the city of Suderham sometimes sneak into the Scumslum section and grab a derelict for dinner, who likely will never be missed.
The Horde boxed set. The monks of the monastery of Punakha Dzong are evil and murderous. Any visitors who are unimportant or unlikely to be missed are captured and held for dark purposes.
The Universal Brotherhood was a cover organization organized by insect spirits and insect shamans. Many UB facilities were set up in run down areas and ostensibly tried to help the homeless, while actually arranging for them to be possessed by insect spirits.
In the supplement Double Exposure, an unholy alliance between the Renraku Mega Corp. and insect spirits exploits homeless people in Seattle, testing experimental medical products on them and changing them into monsters.
Underworld Sourcebook mentions that the SINless (those without a System Identification Number, usually homeless vagrants) are the preferred target of organleggers because they'll never be missed.
In Vampire: The Requiem, a vampire PC can have a trait that give a him or her a safe feeding ground. The first example of such trait is by feeding from the homeless mass in the slum. Considering that vampires can go crazy while feeding and drain the victim to death, it's one of the better traits, correctness aside.
Tabletop Game/KULT supplement Rumours. The Caregiver archetype says that monsters of the Tabletop Game/KULT world feed off of vagrants.
Bloodrayne 2 had homeless people (and sex workers) being kidnapped to be turned into a blood fog (the shroud) that protected vampires from sunlight.
The Thief video game series uses this in the second and third games.
The villain of Thief II : The Metal Age uses the homeless to create his army of Steampunk cyborgs. It is explicitly stated that the nobles don't notice or care, and the victims are being arrested by the Watch, shipped and converted in small groups so that it goes unreported.
The villain of Thief III: Deadly Shadows kills the homeless and absorbs their life force to extend her lifespan. Sometimes she flays them alive to use their skins as a disguise.
Andrei the Tzimice used, among others, homeless people as raw material for his experiments...and his home improvement projects.
In Portal 2, the recorded messages of Aperture Science founder Cave Johnson showed his first batch of Mad Science tests were carried out using the 'best and brightest'. In the second set of tests from years later, his recorded message introduces himself as the man you might know from the 1968 missing astronaut Senate hearings. He is now offering his new batch of test subjects 60 bucks (60 more if they let him "take them apart and install gadgets in them"), and mentions how much nicer the waiting room must be compared with the park benches the test subjects were sleeping on before. In the thirdset of recordings, he's apparently discarded this idea and moved on to testing on his own employees, including himself.
They're allowed to lurk around the waiting room for a whole twenty minutes before and after testing! Luxury!
He also, like the astronauts in the earlier messages, refers to them as "the brightest and the best", before revealing that nope, he couldn't keep a straight face while saying it.
In Assassins Creed I, the "patients" of Garnier's hospital are mostly beggars, prostitutes, madmen, and other homeless taken from Jerusalem by Talal's slave ring. Garnier's plan was to use his drugs to cure their addictions and insanities, followed by training and conditioning them as soldiers, to turn them into loyal warriors in the service of the Templars.
In an episode of Teenage Mutant Ninja Turtles, a super villain called the "Garbageman" abducts homeless people turning them into slaves, referring to them as "human garbage". The police haven't noticed the abductions or perhaps don't even care.
In Disney's Gargoyles, Dr. Sevarius uses Maggie, a homeless woman, in his mutation experiments because nobody will notice she's gone. All of the mutates but Talon (Derek Maza) have no known families.
In one Halloween episode of The Simpsons, Lisa's teacher invites a homeless man into the class on the pretense of offering him a hot meal so the students can see Homer, the new Grim Reaper, reap someone.
One episode of SWAT Kats begins with a homeless guy getting eaten offscreen by one of Dr. Viper's monsters.
Likewise, an earlier episode has Morbulus. He's an interesting case in that he starts out as a villain in his own right, but becomes this trope following his humiliating defeat by the SWAT Kats. After Faking the Dead, he's reduced to hiding out in the sewer where he's found by Dr. Viper, who turns him into the Monster of the Week instead of helping him.