At least one fan grumbled that this was more proof that Carver-led SPN shouldn't be taken seriously (Because obviously, under Kripke the set designers would never, ever have shot a scene that revealed a Winchester brother's blood type without re-watching every episode attentively and Googling anything they might not know about blood types or other scientific concepts to avoid any possible continuity error. Plus we all know the whole Sam/demon blood/Lucifer plot made perfect sense and was a commendable example of ideal continuity.). More interestingly, it led to some fan theories that Dean wasn't John's biological son.
Less interestingly, and predictable in that obnoxious way that fandom can sometimes be, a lot of this theorizing took the form of, "That would explain why John treated him worse than Sam!" This argument is stymied by the fact that John did not treat Dean worse than Sam. (Differently, yes. Worse, no.) And furthermore, the exact nature of Dean's mistreatment doesn't jive with the idea that John valued him less due to the lack of a blood relationship. John didn't only expect Dean to care for Sam and be mature for his age - he also inappropriately relied on Dean as a confidant and emotionally caretaker. Which is to say, he was closer to Dean than he was to Sam. And he often expresses fatherly pride in Dean: see his praise of "That's my man" in Something Wicked, that whole entire speech in In My Time of Dying).
Of course this doesn't prove that Dean was John's biological child - plenty of parents are deeply bonded to their step or adopted children. But it does prove that John's mistreatment of Dean wasn't based on the mindset of a man who resented the presence of another man's son and favored his own birth son.
All these thoughts led me to another possible headcanon: If we choose to disregard the blood type contradiction as poor continuity, why not imagine a scenario where Dean is John's biological child, but Sam is not?
As a non-adopted sister with adopted siblings, I rarely find stories that I can see that part of myself reflected back on me on a literal level. I usually have to rely on metaphor, or on other situations where characters express feelings that I can relate to mine. It's not that there are no stories about non-adopted siblings of adoptees out there. I don't quite remember when Jeremy jumped to nearly to the top of the list of my favorite Vampire Diaries characters, but I'm pretty sure it was after his sister Elena found out she was adopted. Thor and Loki I had some issues with. I saw the first Avengers movie in theaters, and as far as I could tell I was the only person sitting stone faced in that theater while the rest of the audience roared with laughter at Thor dismissing Loki by saying, "He's adopted." I'm always both greedy for and sensitive about literal stories about non-adopted siblings of adoptee, but when I want to see the fullest extent of my feelings, I have to turn to metaphor. I haven't been able to find it in literal representations. Even in non-fiction I've only seen it partially reflected back on me. And I did a lot of reading on the topic.
One such story that appealed to me metaphorically was early seasons Sam and Dean, especially in season two. S4's reveal that Dean, too, had a special destiny disappointed me, because I liked him as the ordinary guy. I could relate to his feelings as the devoted brother of a special sibling, a special sibling whose specialness wasn't necessarily a good thing for the sibling.
So I started thinking, why not make the metaphor literal? Why not have Sam be adopted?
I thought maybe that instead of the usual situation of an unmarried woman placing a child for adoption, Sam's biological parents where married when he was born (and in fact I imagined him an older sister). They placed him for adoption not because of anything about their situation, but because of something about Sam: While his mother was pregnant with him, she was haunted with dreams of her own death, burning up on the ceiling of her unborn infant's nursery. She dreamt of her family stalked by a series of monstrous, yellow-eyed men. It was too late in the pregnancy for an abortion, so she and her husband decided to give the baby up for adoption.
Of course, that contradicts all the stuff about how John and Mary were specifically chosen and brought together for the purpose of breeding Sam (as well as Dean), but hey. When did Supernatural ever take continuity seriously?