The Courier: "You want to attack NCR? All of NCR?"
Father Elijah: "Attack? No, not attack them. Wipe the slate clean. Make the Mojave like it was meant to be... undisturbed by man. I'll send the Cloud, the Holograms. Bring ruin in my hands until only I stand atop the HELIOS One tower again. I'll scour Hoover Dam with the Cloud, rain its walls with spears from the sun... with an army of Old World ghosts behind me, Holograms all. I'll kill them until it's only me, me alone... in a quiet world. In a world that's nothing like what happened at HELIOS One."
—Fallout: New Vegas: Dead Money
- Morpheus is the opportunistic, power-hungry leader of the Children of the Cathedral. Originally a member of the sadistic Rippers, Morpheus left the gang to form his own doomsday cult and eventually joined The Master as the High Priest of the Unity's religious branch. Indifferent towards the Master's teachings and good intentions, and believing himself to be his equal, Morpheus is setting up hospitals with free medical care in towns as a recruitment tool for Unity, luring victims to his church where people regularly go missing and are made into fresh subjects for the Master to use as soldiers in his war against humanity, but not before Morpheus introduces them to the belief that being "baptized" in FEV—Forced Evolutionary Virus—is essential to their lives, a process that can give an excruciating and painful death to those who fail to become Super Mutants, allowing one of his men to "discipline" his believers with a cattle prod. Using his group to make the enemies of Unity simply "disappear", Morpheus shows an interest in destroying the Followers of the Apocalypse, and if his church is set to explode, then Morpheus will run away by himself, abandoning all of his people to die.
- Doc Morbid initially presents himself as merely an arrogant and unpleasant man, but is revealed to be greed personified. As Junktown's resident physician, Morbid offers medical assistance for enormous prices, and is the only doctor in the wastelands to force his patients to pay him for the examination. Those who refuse to pay him are murdered by his two mercenaries and their bodies are taken to his underground lab, where are they are butchered into small pieces and sold to Iguana Bob; the human meat is then cooked to look like iguana bits and given to the population. If Morbid discovers that the Vault Dweller has visited his lab, Morbid will let the player live only if he can remove an eye, declaring that "half of what you have just seen" is now his.
- Frank Horrigan is a Secret Service agent and Dragon-in-Chief to President Dick Richardson. A psychopath even before his mutation, Horrigan delighted in killing whenever he could. His first onscreen appearance has him gunning down a family, including their child, for refusing his demands. Later, he gleefully kills Brotherhood of Steel agent, Matt, and wipes out the entire community of peaceful, talking deathclaws that the player had earlier befriended. Horrigan has a special hatred for "mutants", humans and creatures that have been exposed to the FEV virus or even the slightest amount of radiation. This racism leads to him aiding in the Enclave's plan to unleash a biological weapon which will wipe out all mutated life in North America, in order to make America "genetically pure." Once defeated, Horrigan tries to activate the Enclave Oil Rig's self-destruct sequence, condemning all of his remaining allies to death, just so he can take the Chosen One with him when he dies.
- Dr. Stanislaus Braun is the Overseer of Vault 112 who controls the virtual reality simulation where he and the other vault members reside. A sadist with a god complex, for the past 200 years he's been entertaining himself by torturing and killing every person inside the simulation, only to bring them back to life to torment and kill them over and over again. He specifically mentions that doing so is only fun because they are real people, and not computer simulations. Before Braun allows the Lone Wanderer to leave the simulation, he forces the player to do increasingly horrible things to the other Vault residents, culminating in the deaths of all inhabitants by the player's hands. Braun was also the Director of the "Societal Preservation Program", better known as the Vault experiments. Advertised as providing civilians shelter from the expected nuclear war, in actuality the purpose of the Vaults was to gather unknowing, human guinea pigs to conduct horrific experiments on For Science! These experiments include forcibly turning Vault citizens into Super Mutants, tricking people into ritualistically sacrificing their fellow citizens, pumping hallucinogenic drugs into their ventilation system, and driving people insane by implanting posthypnotic combat suggestions into their minds through white-noise. Most of the Vault experiments resulted in the deaths, or worse, of everyone involved with them.
- Eulogy Jones is the crime boss in charge of the human trafficking occurring in the Capital Wasteland. Killing his predecessor to take his place and establish his own empire at Paradise Falls, Jones oversees everything with an iron fist and rules over the "livestock", keeping them in check by installing explosive collars on their necks; Jones also assigns a homicidal maniac named Forty who enjoys killing slaves with the job of watching them for him. Always in the company of two personal slaves whom he sees as his bodyguards and prostitutes, Jones verbally abuses them on a daily basis and has succeeded in brainwashing one of them, reducing the woman into a subservient sex object suffering from Stockholm Syndrome who would do anything to make him happy; even if she is fanatically loyal to him, Jones is fine with selling her for a thousand caps. Owning a house for captured children, Jones tasks the Lone Wanderer with bringing some "VIP" targets and eventually even more children to Paradise Falls for him to enslave, rewarding you for being complicit in his business.
- Roy Phillips is a rabid anti-human bigot trying to get into Tenpenny Tower through any means possible. When first approached, Phillips's initial plan is to use his feral ghouls to overrun Tenpenny Tower and slaughter everyone inside. Despite this, Roy feels no empathy for his feral brethren, believing them to be mindless freaks only good as guard dogs and cannon fodder. However, if the Lone Wanderer is able to come to a solution where the ghouls are peacefully allowed to move into Tenpenny Tower, Roy will seemingly relent hostilities, at least until a few days later where it's revealed he slaughtered everyone in the Tower anyway, regardless of whether they were anti-ghoul or not, for no reason. When confronted about this, Roy shows no guilt and tells the Wanderer to piss off before he murders the Wanderer too. Furthermore, if Burke is still alive and still plans on nuking Megaton, Roy will fully support Burke's plan so he can see that "smoothskin shithole" wiped off the Earth.
- Vulpes Inculta is the leader of the Frumentarii and the Legion's chief strategist. Becoming a Legionary as a child, Inculta got the position of Frumentarius by disobeying orders and capturing the leader of an enemy tribe. Arriving at Dry Wells, Inculta took over the area and crucified those who resisted along the Interstate 40. Inculta is properly introduced after having slaughtered the citizens of Nipton with a lottery: First place would be spared, second place would be crippled, third and fourth places would be enslaved, and the "Lucky Losers" would be decapitated, crucified or burned on a pile of tires. When Camp Searchlight proved to be a nuisance for the Legion, Inculta ordered Legionaries to commit a Suicide Attack by opening the base's radioactive containers, which not only killed several NCR troops that were stationed there, but also resulted in the ghoulification of the survivors. Disguised, Inculta visited the Strip and planned to chlorine bomb New Vegas with the assistance of the below-mentioned Omertas.
- Cook-Cook is an Ax-Crazy Fiend who is also implied to be a cannibal. The Fiends are a violent bunch of psychos who torture people for fun, but Cook-Cook is so bad that he is barely tolerated even by the other Fiends. He alternates between burning people alive and raping them, such as he did with Corporal Betsy and Pretty Sarah, the latter of whom he disfigured via burning. Two Westsider slavers, who only stopped raping their slaves because it lowered their value, were disgusted when Cook-Cook didn't even wait for them to turn around before enjoying a family he bought from them, starting with their son. One time, he bought some teenage slaves, 3 girls and a boy. The boy was burned alive and the girls made to watch.
- Nero and his right-hand-man Big Sal are the Omerta family bosses. The only rule the Omertas have is "don't go against the family", which is punishable by death, but rather than emphasize loyalty, it is instead intended to keep others from standing in the way of the bosses' plans. Such plans involve secretly working for Caesar's Legion to massacre the entire population in New Vegas as soon as the battle at Hoover Dam begins, with a promise that they'll have control over the city. They are selling out the Mojave to the Legion not because they agree with Caesar's ideals, but because of lust for power and loathing of Mr. House for what they perceive to be his lording over them. They also framed a man for murder to blackmail him into working for them, get their prostitutes addicted to drugs to force them to be dependent upon their bosses, and give them to Clanden to be raped, tortured and killed.
- The aformentioned Clanden is a mercenary and explosives expert working for the Omertas. Though appearing to be a mild-mannered individual, Clanden is in fact a Serial Killer who moonlights as a maker of snuff films. He constructs chlorine bombs for the Omertas—fully-knowing that his actions would kill people in a "fairly large area in a fairly small timeframe"—only if they allow him to videotape himself raping and torturing their prostitutes until they die. When confronted with the evidence of his crimes, Clanden threatens to kill the Courier, claiming to have "nothing to lose", and if blackmailed into leaving New Vegas, Clanden will gladly accept the chance to "find girls to play with somewhere else".
- Dead Money expansion: Father Elijah is the former elder of the Mojave Brotherhood of Steel. His obsession with old-world technology led to him getting his people slaughtered at the battle for HELIOS. After fleeing the battle, he sought out the fabled Sierra Madre Casino, a treasure-trove of lost technology which he wanted to use to "wipe the slate clean." In order to obtain the casino's treasures, he kidnapped dozens of people, attached slave collars to their necks, and blew their heads off unless they acted as Cannon Fodder for the Sierra Madre's defenses. Once the Courier reaches the Sierra Madre, Elijah orders him/her to kill off the allies that had helped them, and later tries to kill the Courier him/herself for outliving their usefulness. Elijah's ultimate goal is to use the Sierra Madre's technology to kill off every person in the Mojave, and then build a new nation where every person will be collared and forced to obey him.
- The Fens Phantom was a notorious, prolific Serial Killer who stalked pre-war Boston. Detached from human society and finding it "exhausting" to fake it, the Phantom made his base in the Fens sewers. Responsible for the deaths of at least thirty people, his victims ranging from the homeless to young mothers, the Phantom mutilated his victims, using their body parts to make twisted art exhibitions with the strong implication that at least some of his victims were alive during the process. Other dismembered parts littered his entire lair or were neatly kept in boxes for future pieces. Discovering a detective was chasing him, the Phantom became obsessed with them. Luring them into his lair, he left tapes walking them through his exhibits, admitting the pride his "work" brought him. Coming out the victor of their confrontation, the Phantom boasted about how much he looked forward to them "having all the time in the world" together now.
- Nisha, from the "Nuka-World" DLC, is the bloodthirsty leader of the Disciples raider gang. A ruthless Social Darwinist who murdered any gang members who refused to follow her leadership, Nisha restructured the Disciples into a gang of hedonistic torturers and murderers. Ever hungering for suffering, Nisha decorates her base and home with the dismembered corpses of her victims, leaving the barely-alive ones chained to beg for freedom. Her most vile achievement is "The Gauntlet", a Death Course into which Nisha throws unsuspecting people to die for the raiders' amusement. "Improving" it to make it more deadly, Nisha shows nothing but joy at the deaths of even the slaves sent in to clean the bloodied tracks.
- Withers is the young leader of a far-right militia staging a coup in the town of Springfield. Declaring Ghouls to be sub-human creatures who deserve to be exterminated, Withers organized an assassination plot to overthrow Mayor Chris Avellone when he began showing a pro-Ghoul political stance, Withers and the ultraconservative activists dressed themselves as Raiders to frame local bandits and killed most of the guards in town before turning Springfield into a slaughterhouse to perform a "genetic weeding", executing all Ghouls that they come across until only pure-blood humans remained while ranting about how they are in the right for believing that "Ghouls are dirty and that's God's honest truth", forcing civilians to isolate themselves to escape from the warzone. When cornered, Withers expresses his hatred and confusion as to why anyone would want to give human rights to Ghouls.
- Thomas Eckhart was a member of the Enclave and the Secretary of Agriculture under the Pre-War Government. Being the last surviving member of the presidential cabinet, he became the leader of the Enclave forces inside the Whitespring bunker. His first action as leader was to hold a vote on whether or not they should continue the nuclear war against China and then had everyone who voted against him looked inside a room that was flooded with Deadly Gas. In an attempt to have the automated control system of the Appalachias nuclear silos raise the DEFCON Level and give him access to nuclear missiles, he unleashed Liberators and Super Mutants onto the survivors on the surface. When this wasn't enough, he also released the Scorchbeasts, which would eventually whip out most of the remaining human population in the region. Despite being long dead by the time the game takes place, he left behind a region devoid of human life but full of dangerous creatures.