Original manga and Brotherhood:
- Shou Tucker transforms his own daughter and her dog into a Half-Human Hybrid, partly to see if he can and partly to retain his State Alchemist status. He had previously done the same thing to his wife. He's the only character who even comes close to evoking Al's rage, and what he did leaves a stain on the Elric brothers' memories for the rest of their lives. Making Tucker even more abhorrent is his complete refusal to own up to what he did. He acts as though the Elric brothers shouldn't have a problem with his actions, assumes that anybody else would have done the same thing, and when thrown in jail, spends all of his time whining about how "nobody understands" that he did it For Science!. Destroying his family because he was either too lazy, or too devoid of talent to come up with another way of keeping his status, Tucker is one of the few characters in the manga to possess absolutely no redeeming traits or sympathetic moments.
- The unnamed and utterly heinous Dr. Goldtooth is essentially Tucker with talent. This gold toothed doctor crosses the Moral Event Horizon in one of Bradley's flashbacks, when he's shown cackling with glee as he puts one subject after another through the process intended to create Wrath—a process which horrifically kills the first twelve candidates, deconstructing their bodies while they are still alive. In the present day he only gets a few scenes, but they are more than enough. He uses his medical alchemy to heal Mad Bomber Solf J. Kimblee so that he might be unleashed upon the heroes again. He later looses the remaining Fuhrer candidates (all of whom have been reduced to an essentially mindless state) on Ed, Roy, Hawkeye, and Scar to prevent them from interfering with Father's plans to destroy the country, activates the Transmutation Circle that sends Ed, Al, and Izumi into Father's presence, and finally has one of the candidates slit Riza Hawkeye's throat in an attempt at forcing Roy to perform human transmutation and open the Gate. Perhaps most importantly, he's privy to Father's endgame (unlike Central Command, who believe they are all going to receive immortality) and simply doesn't give a damn. No explanation for his actions is ever given, and he spends all of his appearances sporting a Slasher Smile and bragging about his achievements as a scientist.
- The Sacred Star of Milos: Security Chief Atlas killed the movie's female protagonist's parents, then stole her brother Ashley's skin and used it as a disguise in order to trick the rebel group, Bats, into making a Transmutation circle for him in order to gain power to rival other nations. He then killed the Bats' leader, Miranda, for her sacrificial blood, murdered his co-conspirator to gain his blood as well, and sacrificed dozens of Amestrian soldiers by "feeding them" to Milos's machinery to create a Philosopher's Stone for himself.
- Dante is a 400-year-old woman with a penchant for Body Surfing; she's stayed alive this long by jacking innocent people's bodies, ditching them when they start to rot, and repeating the process infinitely. When her own Philosopher's Stone runs out, she sets in motion a plan to cause so much misery in Amestris that someone will be desperate enough to recreate the Stone, allowing her to steal it with no risk to herself. She's abusive towards her Homunculi "children", arranges for Ed to kill Greed, jacks her own assistant's body, and finally, attempts to steal the body of one of the hero's Love Interests, who had already been severely traumatized by rape/pregnancy, solely so that she can force him to have sex with her. Said hero is both a teenager, and her ex-boyfriend's son. She later shatters the mind of one of her Homunculi servants when he dares to miss his dead friend, turning him into a mindless eating machine. She's never shown in a sympathetic light, comes off as an overconfident Jerk Ass in person, and doesn't even have the excuse of not being human to protect her.
- Envy’s manga counterpart was pitiful enough in the end to avert this trope. This version however is a malevolent sadist who gets his kicks out of ruining people's lives (joining up with his Big Bad mom solely so he can kill as many people as possible), abusing both the other Homunculi and anybody they've managed to take prisoner, and making liberal use of the Shape Shifter Guilt Trip, taking on the forms of people's loved ones before attacking them. He crosses the Moral Event Horizon with Hughes' murder and then follows it up with a string of murders and mind games that end with his killing Ed. He's got Parental Abandonment as a Freudian Excuse, but it doesn't come close to justifying his homicidal mania, and he ultimately undermines it when he kills his father rather than trying to reconnect with him.
- King Bradley/Pride is already a military dictator. He gets worse when it’s revealed that he's the one who ordered the genocide in Ishbal, and worse still when he has those actions repeated in Liore, with the intent of leading his own nation to destruction. Then he crosses the Moral Event Horizon with his cold-bloodedly nonchalant murder of Marta and throttles his own son, who had served as his Morality Pet, to death in the finale, while ranting about being an agent of God, thus establishing himself firmly as an irredeemable bastard.
- Solf J. Kimblee, unlike his manga counterpart, is a Psycho for Hire, Nietzsche Wannabe, and Misanthrope Supreme par excellence, who Loves the Sound of Screaming and isn't afraid to share it with you. He committed genocide in Ishbal, tortured Scar by blasting him apart one piece at a time, blew up his fellow prisoners in order to escape from prison, betrayed Greed to Frank Archer, tries to murder Al soon after his reinstatement, reenacts the Ishbal genocide in Liore, and finally dies while trying to take Al and Scar with him, succeeding in killing Scar. Kimblee is a truly appalling mix of rage, hatred, and pure nihilism.
- Barry the Chopper, unlike his manga incarnation, is far more vicious and horrifying. Barry was once a simple butcher living in Central City who had grown bored with his life of cutting up pigs and cows. One day, to see what it felt like, Barry decided to chop up his wife and quickly found that he loved the sensation. What followed was a string of women being brutally murdered. Barry's killing spree came to a temporary halt when he was arrested after trying to kill the Elrics' childhood friend, Winry. Rather than be executed, Barry was experimented on, had his soul bound to a suit of armor, and became one of the guards for the Fifth Laboratory. After the lab's destruction, Barry slaked his bloodlust by joining a group of mercenaries to slaughter a camp of harmless Ishvalans. An utter sociopath, Barry killed people for no other reason than because he enjoyed it. When asked by Alphonse if Barry was afraid that he wasn't the real Barry and was just an artificially constructed soul, like Barry accused Alphonse of being, Barry stated that it didn't matter if he was the original Barry or not* . Barry claimed that so long as he had the ability to kill people, he loved who he was: "I kill therefore I am."