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- Vandal Savage may have been Cain and forgotten.
- Over at DC Comics, it has been revealed that The Phantom Stranger is Judas Iscariot. In this case he's actually repented since then, and has spent the past two thousand years helping people from the shadows as penance.
- In The Unwritten it's pretty clear that Pullman is Cain as well as some other mythological bad guys.
- Adam is a Ghost Rider villain who felt bad about the whole original sin thing, and so plotted to use Ghost Rider's powers to burn sin out of the world.
- In Society of Super-Heroes: Conquerors of the Counter-World #1, Vandal Savage of Earth-40 is heavily implied to be Cain, with the meteor that gave him his powers being the rock that he used to kill Abel.
- Cain from The Strange Talent of Luther Strode is explicitly the biblical Cain.
- In one of the 90s Harris stories Vampirella fights the "Black Pope of the Vampire Church", who turns out to be Judas Iscariot.
- The Blood Red Queen of Hearts was body-hopping demoness who was identified as the Whore of Babylon.
- Lilith, the first wife of Adam, also used to be a malevolent figure who gave birth to many demonic races and monsters. But she has since repented and turned into The Atoner. Or so she has lead others to believe and remained evil as ever.
- The Librarian has Judas as the first vampire.
- In Dracula 2000, Dracula is Judas, who is also the Wandering Jew, a legend of a man forced to Walk the Earth very clearly based on the story of Cain. Interestingly, the way to kill him is to re-create the conditions of the incomplete hanging that caused him to be trapped between life and death.
- He Never Died features Cain as the main protagonist, still alive in the modern day.
- Grendel is sometimes portrayed as Cain in later adaptations. What we have of the original was rewritten to include Christian elements, so this isn't particularly surprising (though the wording it uses would imply a descendant of Cain).
- Not a direct example, but The Knights of the Blackened Denarius in The Dresden Files get their powers from 30 silver coins, each with a fallen angel inside. The coins are heavily implied to be the Thirty Pieces of Silver that Judas was paid to betray Jesus. Nicodemus, leader of the Knights, also wears the noose Judas hung himself with as a necktie; it offers him protection from anything. Except, as Harry finds out when he tugs on the end of it, itself.
- Please Don't Tell My Parents I'm a Supervillain gives us Lucyfar, a sorceress who claims to be the Archangel Lucifer, Princess of Darkness. Most people think she's crazy or lying, but she is surprisingly powerful when she gets serious. The crown of black fire, especially, is the kind of thing that makes you re-evaluate your assumptions.
- Played with in José Saramago's Cain. Since God has ordered that Cain cannot be harmed by any living being - including Himself - Cain gets to live through all of the Old Testament, bitter at being turned into the first murderer because he, unlike his brother, didn't want to spill blood to appease God, and horrified by the events of the OT becomes convinced that God Is Evil. He spends a lot of time calling the old man out, before eventually hitching a ride on Noah's ark. When all of humanity but God's chosen survivors have drowned, Cain takes out Noah and his family Slasher Movie style, leaving God alone with an empty world. End of creation.
- In Supernatural, Cain killed Abel to prevent his brother from being corrupted by Lucifer and then became one of the first demons. He was the first Knight of Hell and trained all the others, including Big Bad Ensemble member Abaddon. He then fell in love with a human woman and had a Heel–Face Turn. After she was killed by Abaddon, he slaughtered most of the other Knights and went into hiding. Dean and Crowley accidentally track him down when they search for a weapon that can kill Abaddon.
- Biblical bad guys make up about 90% of the villains on Supernatural, with Lucifer being the bad guy for two seasons and various demons and angels making up the rest. Archangel Michael, while technically a Well-Intentioned Extremist, was actually just as bad as Lucifer. The Four Horsemen of the Apocalypse were also major villains, with the character of Death recurring every other season or so. Death wasn't a bad guy, but the other three definitely were.
- Jesus Christ Superstar deconstructs Judas.
- In Vampire: The Masquerade, the first vampire is named "Caine" and is the Cain from the Bible. In Demon: The Fallen (in the same universe), it's noted that Caine invented murder and the killing of sentients.
- Though in the vampire mythology Caine was the Messianic Archetype who righted wrongs and punished the wicked.
- Cain is also alluded to in the Video Game Vampire: The Masquerade – Bloodlines. Apparently, he spends his eternal afterlife working as a cab driver in Downtown LA. Playing as a Malkavian, you realize this when you eventually meet him. You would Go Mad from the Revelation, but, y'know, you already are.
- According to the in-universe Vampire scripture The Book of Nod, Caine spent a good amount of time with Adam's first wife Lilith, who taught him all about the Disciplines. It's not quite clear what she is, but she definitely had some sort of supernatural power and probably wasn't a Vampire herself, at least not in the same way that Caine was.
- Orpheus suggests she might be Grandmother.
- In Hunter: The Vigil, Nimrod is portrayed as one of the first slashers.
- Naoya in Devil Survivor is a reincarnation of Cain, punished by God to be reborn every time the old body dies, and has the memory of every life time he has lived ever since his first life. Over his long life he has become obsessed with revenge and seeks to achieve that by having Abel, the player character, rebel against God. Granted, this is Shin Megami Tensei, so YHWH kinda deserves it. It is implied in Overclocked that YHWH manipulated Cain into killing Abel.
- It is hinted at that the Nod commander Kane in the Command & Conquer: Tiberian Series is... Cain. Evidence for indicates that he is shown to be the same age during the 1940s, he survives an Ion Cannon blast that he embraces and when assumed to be be the Biblical Cain by followers does not deny it. Command & Conquer: Renegade confirms it, since you find Abel's tomb beneath the Temple of Nod. In the rather poorly received final chapter known as Command & Conquer 4: Tiberian Twilight, it is revealed that Cain is actually an alien stranded on Earth for the past thousands of years, and has likely shaped the advance of civilisation to reach a point when he can leave the planet. He phoned home at the ending, leaving through a portal left by a failed Alien Invasion.
- In Assassin's Creed II, it's revealed in the optional glyphs that Cain killed Abel over a Piece of Eden and was the founder of the Templar Order.
- Subverted in the SCP-verse. Cain is actually a nice guy (and in this world, that's saying something) and The Atoner, only harmful to plants due to his Enemy to All Living Things status. His brother Abel on the other hand, is a Blood Knight. It's suggested that their lives for the past few millennia have changed them.
- It's implied that Abel only died because of Cain's Attack Reflector that he can not turn off.