- Complete Monster: Alex Cross has faced many revolting criminals, but these stand out as the worst:
- Kyle Craig, or The Mastermind, is a former FBI special agent and Alex Cross's Arch-Enemy. A violent individual since childhood, Kyle was responsible for multiple killings even before joining the FBI, including that of his own brother. As the Mastermind, Kyle perpetrates a series of bank robberies followed by murders in Roses Are Red, making sure to dispose of his accomplices, and raping the women he had hired post-mortem. While his partners at the FBI are busy investigating the murderous robbers, Kyle rapes and kills a woman in a home invasion, and then sets his eyes on Alex's girlfriend, committing the same crime with her and mutilating the body afterwards. Kyle calls Alex to inform him about the horrendous death of his girlfriend, just so he could hear his reaction. Realizing in Violets Are Blue that he has been exposed, Kyle attempts to kill Alex's partner and later a woman he had saved from another killer, but is arrested and sent to death row. Assuming the identity of his attorney in Double Cross, Kyle escapes and kills his mother, using her money to travel around the world and murder more people, including the judge who had sentenced him to death. Failing to kill Alex, Kyle returns years later in Cross Fire, this time posing as a FBI agent he had killed who had been assigned to work with Alex. Seeking to hurt Alex's loved ones, Kyle attempts to take his family hostage, and commits suicide upon defeat, dying in confusion to why Alex did not kill him. A merciless Serial Killer with an obsession for female bodies and being Alex's shadow, Kyle was one of the worst criminals Alex had to face in his career.
- Gary Soneji, real name Gary Murphy, is one of Alex Cross's earliest and most personal foes. First appearing in Along Came a Spider, Soneji is a depraved killer who claims to have killed over 200 people, and starts the book by brutally murdering two black families, mutilating the women and even killing an infant. Longing to become the most infamous criminal mastermind in modern history, Soneji duplicates the Lindbergh baby case by abducting two private school children, fully intending on burying them alive while he disappears without a trace. Killing the FBI agent in charge of the case as well as a schoolteacher, Soneji has a breakdown after his plan goes awry, and takes a McDonald's restaurant hostage, killing an innocent man and a cop. Upon his capture, Soneji quickly plans his escape, and once he's free he attempts to murder Alex Cross's family for revenge. Returning once again in Cat and Mouse, Soneji, feeling he has nothing to lose due to contracting AIDS in prison, decides that the whole world deserves to be punished for his misfortunes, and goes on a cross-country killing spree, slaughtering innocent men, women, children, cops, and even his own wife; he leaves his young daughter alive, but tied up in his house's cellar to slowly die of starvation. When confronted by Cross yet again, Soneji takes a bus full of innocent people hostage with a bomb, and abducts a baby to ward off the cops before attempting to beat Cross to death for "ruining his life". A relentless and utterly unstable murderer who longs to top other killers in sheer brutality, Gary Soneji would stop at no limits to feed his pathological need for attention.
- Geoffrey Shafer, known by law enforcement as the Weasel, is one of Cross's most personal enemies. A diplomatic staff member moonlighting as a Serial Killer, Shafer is playing a "game" with a few other men that he meet at the MI-6, who style themselves after The Four Horsemen of the Apocalypse, with Shafer playing the role of Death. He is introduced in Pop Goes the Weasel, when he finds a prostitute and brutally kills her. He then puts on blackface, goes out in a cab, picks up a woman and murders her. He later goes out again, finds a man, and kills him too. Shafer stalks George Bayer, who plays Famine in the "game", murders the women he solicited, and leaves the bodies in a compromising position. Realizing the police are on to him he goes south to Maryland and kills a mother and her teenage daughter. Shafer then targets DC Detective and Cross's love interest Patsy Hampton and brutally kills her. Cross arrests him, but evidence being inadmissible due to diplomatic immunity means he gets acquitted. Shafer then kidnaps Cross's fiancée Christine. He murders the other players of the "game". After a fight with Cross he apparently dies, but resurfaces in Europe and kill his wife. He reappears in London Bridges living in Brazil. Here he continues his murderous hobbies until The Wolf uses a streetwalker to draw him out, kidnap him, and get Shafer to work for him. Shafer bombs an army base, and then meets a sniper and has her kill the CIA Director. He later goes out and kill another prostitute. After that he goes and confronts his sister-in-law and children. He threatens them, asks them for a kiss, and when they refuse he only refrains from killing them because he states that he "does not have permission" to kill them.
- Draco in Leather Pants: Some interpretations of the Mastermind.
- Moral Event Horizon: Geoffrey Shafer starts out as somewhat likable in an evil way until a certain point, but crosses the line with the murder of Patsy Hampton.
- Kiss the Girls. One scene in particular involves Casanova using warm milk to lead a live snake into the rectum of one of his victims. Many reviews cite this scene as so disturbing it ruins the entire novel. note
- The lovingly detailed description of The Mastermind having sex with a corpse in Roses Are Red.
- Four Blind Mice has three contract killers (hence the title), and one of them is described as getting hard at the memory of murder.
- I, Alex Cross has Zeus, who possibly tops Casanova in terms of being a disgusting murderous sex fiend.
- Complete Monster: The sadistic "Picasso" is an assassin who was hired to eliminate Giles Mercier and his associates Fan Yau Lee and Erich Nunemacher. After being invited to Fan Yau's house, he proceeds to sedate her with a paralyzing drug. Afterwards, he murders all of her bodyguards and tortures her to death by cutting off all of her fingers. He later goes after Nunemacher, but fails to kill him due to Alex Cross and his partners Monica and Tommy interfering. As punishment for their interference, Picasso breaks into Monica's apartment and tortures her to death, shortly before sending a photo of her body to Cross's cell phone. Picasso then makes it personal by murdering Maria, Cross's pregnant wife, and later calls him after her funeral, telling Cross that the only reason why he killed her instead of him was so he could make him suffer. Picasso then goes after Giles Mercier, attacking his convoy with a rocket and killing several police officers, along with Nunemacher and Mercier's double. During Picasso's final confrontation with Cross, Picasso subdues Cross and attempts to inject him with the same paralyzing drug as well.
- Casanova can be found at Kiss the Girls.
- "Funny Aneurysm" Moment: Tommy jokes shortly after finding Fan Yau's safe that he'd want Cross to be wrong at least once. What are Cross' first words to Tommy after his wife is killed?
Alex Cross: (tearfully) "I got it wrong, man..."
- He Really Can Act:
- Matthew Fox shows some real impressive acting chops as Picasso.
- Likewise, Tyler Perry is pretty impressive in the dramatic moments.
- Narm: The tagline "Don't Cross Alex Cross" is a rather laughable use of the character's name.
- Nausea Fuel: Picasso's first victim had all her fingers cut off and she could feel it all without reacting.
- One-Scene Wonder: Giancarlo Esposito's (Breaking Bad and Revolution) quick scene as Daramus Holiday, the uncle of a teenager about to be convicted for murder.
- Squick: Alex using the first victim's severed thumb to open her safe.
- Tear Jerker: Alex's wife getting killed by Picasso and especially the scene where he tries to comfort his daughter over her mother's death, relating it to his own father's death, which makes it even sadder.
- They Wasted a Perfectly Good Character: Some viewers were upset that Monica Ashe was killed off and then forgotten about, mostly since she was the film's only Action Girl who was portrayed by a relatively good actress and had an ongoing subplot with Tommy.
- WTH, Casting Agency?: Many people raised an eye brow when it was announced that Tyler Perry would be playing Alex Cross, though some critics did praise his acting.