Since the playable characters have so few canon traits, there is a lot of room for fanon.
Back to YMMV.
- The demonic characters are drawn with extra Big Red Devil traits like tails, fangs, hooves, claws, and so on.
- Maggy is often depicted as a Big Eater and chubby, due to her starting with Yum Heart and her having Thunder Thighs and Bucket of Lard in The Tank challenge.
- Maggy and Eve will often be friends, since they were the only female human playable characters until Repentance introduced Bethany several years after Eve's debut. They'll often be opposites in terms of personality, with Maggy being more positive and Eve being more cynical.
- Eve is considered to be a self-harmer due to her starting with Razor Blade.
- Cain often has a Money Fetish due to his unlock requiring you to have 55 coins. He's also Born Lucky due to him starting with Lucky Foot.
- Samson's Bloody Lust is interpreted as him having a Hair-Trigger Temper.
- Eden was confirmed by Word of God to have No Biological Sex, but fandom usually refers to them as male anyway. They always have their signature glowing white eyes, even though these canonically only appear in one cutscene. They are also often considered to be an angel, especially before the addition of Apollyon when there were no playable angelic characters.
- Lilith is usually the Team Mom and sometimes the parent of Incubus or another familiar. She may also be a succubus.
- Satan is sometimes considered to be Azazel's father, with Lilith as his mother. Sometimes Eve and Judas/Dark Judas are also Satan and Lilith's children.
- Azazel may also be in conflict with Satan, with him either trying to protect Isaac from Satan or competing with him for the rule of Sheol.
- Azazel will either be the Token Evil Teammate or a Jerkass, or in complete contrast to this, he'll be a Nice Guy with the Face of a Thug. Sometimes these two aspects are combined to make him Innocently Insensitive or a Jerk with a Heart of Gold.
- If Azazel is a Nice Guy, he'll often have an obvious crush on someone, which may or may not be requited.
- Apollyon's resemblance to Gnawed Leaf's statue form has led people to speculate that he's made of stone or is a gargoyle.
- Brother Bobby and Sister Maggy are sometimes considered to be Isaac's aborted siblings.
- Canon is a little bit vague on what Brimstone actually is, with its only description being "blood laser barrage". In fanon it's either drawn as a beam of red light or as a stream of blood, going with either the "laser" or "blood" interpretations. Less commonly, it may be a stream of molten sulphur to relate to its name. Repentance came with the Sulphur item, a three-room charge active that gives Brimstone for the current room, giving credence to that last point.
- Since the introduction of The Horny Boys in Repentance, Loki and Hornfel are commonly considered to be brothers. Canonically, they are artificially conjoined and so they may not even be related.
- The popular "Chatty Keepers" mod (which adds random dialogue to shopkeepers) adds in a headcanon that Keeper himself is the Benevolent Boss of the regular shopkeepers, who are all overjoyed to see him whenever he visits and buys their wares.
- In a similar manner, since shops always have one shopkeeper, or in rare cases, Greeds, Greeds are depicted for a long time to be the only other sapient civilization in the depths before Repentance added Gehenna and Mausoleum, both are populated predominantly by cult-themed enemies.
