Catherine "Cat" Crawfield-Russell, Crispin "Bones" Russell III, and their allies have faced numerous opponents—whether demonic, undead, divine, or mortal—but the following threats have proven themselves to be a special breed of diabolical.
- Halfway to the Grave: The Human Trafficking network is a nebulous criminal conspiracy headed by a vicious gangster and backed by a corrupt Ohio public official:
- Hennessey is a Master Vampire who functions as the ringleader of the human trafficking network backed by Governor Ethan Oliver. Adopting a veneer of geniality, Hennessey works with his co-conspirator to capture vulnerable women—including drug dealers, drug addicts, vagrants, and prostitutes—forcing them into wretched lives as involuntary prostitutes, blood producers, and human livestock. Feared by subordinates and associates alike, Hennessey subjects those who would betray him to slow and painful deaths, with one informant committing suicide rather than face Hennessey's wrath. Discovering Cat Crawfield's identity as his attempted killer, Hennessey kills the former's grandparents and captures her mother in order to lure her into a trap alongside his nemesis, Bones Russell. When Cat and Bones confront him, Hennessey mocks the latter for his constant pursuit.
- Governor Ethan Oliver is the benefactor of the human trafficking network, and a sleazy, corrupt, and ambitious figure who hides under a good reputation. Originally frequenting brothels in order to rape women, Oliver eventually begins colluding with Hennessey—destroying any documents relating to missing women captured by the human trafficking network, and having the destitute and disenfranchised trafficked—in order to further his own political career. After his co-conspirator is eliminated, Oliver has a hospital bombed to eliminate the rescued victims in a bid to silence them. When confronted by Cat Crawfield, Oliver holds her at gunpoint, and boasts about his intentions to become the President of the United States, as well as to continue the process he started.
- Destined for an Early Grave & This Side of the Grave: Apollyon, originally Malcolm Untare, leads a massive cult of ghouls in hopes of starting a species war with the vampire community, viewing vampires as inferior to ghouls. Apollyon incited hatred against vampires in the 1400s, having claimed that Joan of Arc would become the most powerful undead creature in existence if she became a crossbreed of a ghoul and a vampire. Repeating his rhetoric against Cat Crawfield-Russell centuries later, Apollyon encourages his cultists to murder vampires who lie outside the protection of a Master Vampire. Furthermore, Apollyon habitually recruits younger followers in a cruel and unusual fashion, having their tongues removed before murdering them and turning them into ghouls. During the final battle, Apollyon intends to publicly execute Cat in order to consolidate his power. After being defeated in battle, Apollyon begs for undeserved mercy upon being sentenced to death for his crimes.
- One Grave at a Time: Inquisitor Heinrich Kramer is the religious zealot and misogynist turned malevolent spirit who wrote a treatise on witchcraft which motivated centuries of witch hunts and burnings—having himself sentenced many innocent women to death—as well as a prolific rapist and murderer. Having previously tormented anyone who sensed his ghostly presence to the point of suicide, upon achieving the ability to become tangible on All Hallows' Eve, Kramer seeks out an accomplice, has the pets of his prospective victims murdered, then rapes and burns his victims before murdering his accomplice. Summoned by a medium on behalf of Cat Crawfield-Russell and Bones Russell, Kramer attacks the group, stalking and harassing Cat multiple times, culminating in a bloody confrontation with several paranormal division personnel. Targeting Cat, he captures two other women and forces Cat to allow him to capture her for a chance to free his other victims, a promise he has no intention of keeping.
- Up from the Grave: The new director of the Paranormal Unit and his financier inflict gruesome experiments against vampires and ghouls for nefarious purposes:
- Jason Madigan, the successor to Donald "Don" Williams as Director of the Paranormal Unit, initially presents himself as a smarmy bureaucrat, but eventually shows his true colors as a cruel sadist who has experimented on thousands of ghouls and vampires in the hopes of creating a hybrid Super Soldier backed by former White House Staffer Richard Trove. To this end, Madigan had misappropriated DNA from Cat Crawfield-Russell, as well as from an unidentified soldier, forcibly impregnating a human woman with the embryo, the only embryo out of a hundred to survive pregnancy. Once the child, Katie, is born, Madigan had experimented on her and subjected her to brutal conditioning, successfully turning her into a ghoul/vampire hybrid and a ruthless Child Soldier. When Cat discovers that the Paranormal Unit is missing and arranges to meet up to discuss their disappearance, Madigan leads her into an ambush before taking her to his facility, where he attempts to experiment on her. When Cat escapes, and confronts Madigan alongside the freed captives, Madigan vindictively swallows a cyanide pill in order to deprive Cat of the information leading to his backer.
- Richard Trove, the former White House Chief of Staff, is Jason Madigan's shadow backer, and a power draining demon who wants to start a war between vampires and ghouls so that his own species may reign supreme once more. To this end, Trove had encouraged Madigan to perform genetic experimentation on both species, supervising the Behavioral Conditioning of the resulting test subject, Katie, turning her into a vicious killer despite her young age. When confronted by Cat Crawfield-Russell and Bones Russell, Trove taunts Cat with the knowledge that Katie is her daughter. During the final confrontation, Trove attempts to incite the ghoul population by invoking Apollyon's rhetoric. Trove proceeds to attempt to drain Cat of her energy, only to be stabbed in the face with a demon bone knife.
Night Huntress World
- "Devil to Pay": Xaphan is a primordial being who makes a habit of possessing people and driving them to violence. Having taken possession of Blake Turner after his previous host ran in front of a car, Xaphan regularly forces Blake to commit murder, occasionally having the incidents recorded in order to taunt Blake. When the vampire Elise, along with Cat Crawfield-Russell and Bones Russell, are in the midst of bringing Blake to their sire Mencheres to see if they can save him, Xaphan taunts Cat using the voices of her deceased grandparents. In his first encounter with Mencheres, Xaphan refuses to leave Blake's body, preferring to inflict whatever suffering he can before the latter expires. Realizing that he is trapped in Blake's body, Xaphan tries to force Elise to negotiate with him, threatening to kill the vampires and Blake if they trap him in the Bonneville Salt Flats.
- Once Burned, Twice Tempted, & Bound by Flames: Mihaly Szilagyi, the Hungarian noble turned vampire, is Vlad Tepesh's father-in-law turned nemesis. Having previously imprisoned Vlad under inhumane conditions, Szilagyi had made a false alliance with Vlad claiming to want to reclaim Vlad's native Wallachia from the Ottoman Empire, but actually colluding with the Ottomans and causing thousands of deaths. Seemingly dying at Vlad's hands after killing the latter's heir, Szilagyi eventually resurfaces in the 21st century, attempting to abduct the psychic Leila Dalton multiple times, burning a crowded nightclub and endangering several patrons to that end. Eventually capturing and torturing Leila and her mentor Marty, Szilagyi fakes his death once more by destroying a medieval castle formerly belonging to Vlad. Having a subordinate target a crowded carnival to attack Leila—subsequently massacring Vlad's household and destroying a mountain, killing several more—Szilagyi eventually proceeds to capture and flay Leila, intending to have her raped to antagonize Vlad. Thwarted by an infiltrator, when a recovered Leila and furious Vlad come to Slovenia to confront him, Szilagyi has their plane sabotaged, killing even more civilians.
- Shades of Wicked & Wicked Bite: Dagon is an eons-old demon who makes deals with mortals for their souls. Discovering the immortal child Veritas in ancient times, Dagon subjected her to repeated Human Sacrifice and other horrors, exploiting her ability to resurrect. Using the resurrection of Veritas to create a religion in his name, Dagon tricks hundreds of innocents into giving up their lives to him with false promises of resurrection. Prevented from inflicting further torment, Dagon begins a campaign of bartering and capturing the souls of mortals before consuming and extinguishing them within himself to increase his power. Dagon torments Veritas in the present and begins a quest to utterly ruin her life, later killing dozens of newly resurrected innocents to return himself to power, intending to make his enemy Veritas suffer.
- Wicked All Night: The Deity Triumvirate, who originally ruled over the world as tyrants, wish to combine their powers and recreate the world in their own image, no matter how many millions die in the process:
- Phanes is a deity with the ability to control illusions. Previously with his fellow gods, Phanes had sold them out and took the credit for their deaths by killing their opponents in order to achieve a good standing in the supernatural world. Bored with his current standing, Phanes tricks Veritas into helping unleash his fellow gods Morana and Ruaumoko. The three, led by Phanes, unleash a wave of destruction on the planet.
- Morana is a frost deity who views mortals as bugs. After being freed from the Underworld by Phanes, Morana attempts to manipulate the ghoul population into going to war with the vampire population for her cause. When they refuse, Morana unleashes her frost powers in an attempt to wreck New Orleans, leading to the deaths of nearly a 100 people.
- Ruaumoko is a fire and earth deity. After being freed from the Underworld, Ruaumoko begins a wave of destruction, starting with his native New Zealand, which he attempts to level with an earthquake. Maintaining an utter hatred of vampires due to them defeating him, Ruaumoko attempts to set off a volcano near the Vampire Council in Athens, despite the fact that thousands could die.