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What if Supernatural was the American Dr. Who?
That's not just idle speculation, that was the quote from one of the show runners back in 2014:
I joke, “Why not become the Doctor Who of America?” Let’s turn around, take the boys as long as they can and eventually find two other hunters. I don’t know if anybody likes that idea outside of me, but I think it’s the kind of show that speaks to people and can keep going for quite a long time.
Now I'm not actually that opposed to the idea completely. I think there's something very Americanish about Supernatural and the foundational world it established is pretty solid with a lot of possibilities for expansion.
But Dr. Who has survived for 50ish years because the creators of it invented a brilliant in-story reason and tradition for replacing the actors. While J&J have been at this too long, making the SPN brand pretty much undeniably synonymous with their characters, there was an opportunity there once to do what Dr. Who did. What if, when a new show runner took over, they brought in new protagonists?
Heck, since this season involves Jack and alternate worlds in Supernatural itself, let's just imagine what that other world might look like, starting with the Sera Gamble years...

Season 6

When the show was turned over to Sera she had the bold idea of changing out the protagonists themselves and growing the possibilities from the roots Kripke laid down. They took very little time off in order to best find and get the new characters. Behind the scenes documents detailed how they didn't want to make the new protagonists too different (i.e. a half dozen lesbians) because then the audience wouldn't accept the season as part of the brand and ask why they didn't bother with a whole new show. On the other hand, Sera was concerned that making the changeover too identical (i.e. two good-looking straight brothers) would also be rejected by the audience as they ask why bother with the change at all. In the end they went with a straight, married couple. It was a little different, and a little same. It also had the advantage of married hunting couples having being established previously in the show. In fact given the ending of S5 is Dean settling down with Lisa (in this world there is no closing shot of Sam) one could argue that the audience is already expecting a married hunting couple so it wouldn't be too much of a shock. They also went with the obvious back-story of being put on the hunting path by having a child that monsters killed.
Episode 6.01 and 6.02 started the season as a two-part hand-off episode involving Dean and our new protagonists. The monster itself was still a d'jinn and they used it's abilities to tell a drug metaphor in the suburban neighborhood. By the end the couple is pretty well established but their vehicle (an old van) is destroyed. Dean decides he's definitely through with the life and hands them the keys to Baby, making her SPN's TARDIS.
From there we had episodes connecting the couple to the secondary cast. Castiel and Crowley both got their own episodes where they too "meet" the new protagonist and establish that they'd be cleaning up the aftermath in Heaven & Hell and won't be around much. 6.04 is pretty similar to our version with the couple meeting Bobby and helping him out with his deal with Crowley. After that are some episodes that appear to be MotW but are later revealed to be a part of the arc. The Twilight spoof episode happens later on where the couple agree to have the husband become a vampire as an undercover effort to learn what's going on. The French Mistake is still the 15th episode, but this time it's about the couple learning about the Winchester Gospels. Jared & Jensen return to do guest spots in segments representing the couple reading a "lost book" (a book that Chuck published but we never saw on the show) which relates to a case the couple is working. It had a real touching finale where Dean (in reality this time) finds a gift basket of alcohol at his door with a picture of Baby and a note assuring him she's well taken care of and "thank you" for all him and his brother did.
So what's the arc for the season? Well it seems that with the apocalypse done last season, the monsters decide it is their turn to have an apocalypse - only they don't all agree on which one. The largest faction of monsters seek to bring forth the Mother, Echidna (not Eve like we're sued to). While she is mother to a LOT of monsters, she's not responsible for all of them. In the middle of all this arc Echidna does arrive but the twist is that she's not really interested in ending the world, she's just annoyed at the number of her children that were killed by demon/angel crossfire in the previous season. She also reveals that Purgatory is divided into territories and there is something much worse and much older in there: Leviathan. The couple kill her anyway which turns out to be what another monster faction needed to release the Leviathan...
Season 7
This season is the most like ours save there's nothing in it about Sam's mental illness. Leviathan come and begin a different plot to "end" the world. The biggest twist is that it wasn't exactly their idea. Several monsters volunteer to be their "cultists" and in one episode the couple come to terms with their child's death and that not all monsters are evil when they help free a vampire named Benny from the Leviathan he was serving (the alternate episode of 7.16). Later on in the season, we discover some humans are also serving the Leviathan (after all, they're offering free healthcare). In fact a human named William Kane (this world's version of Dick Roman) is the one who gave the leviathans the idea of conquering the world by domestication, the head Leviathan is really his manservant.
There's twists and turns through the season as we expect. This time the wedding episode (#7.08) is really the couple's efforts to renew their vows in Las Vegas only for everything to go comically wrong. Frank is introduced when Bobby has to "retire" for a little while. Repo Man (#7.15) is the annual reunion with Dean coming back to the show to help the couple deal with a demon returned and his possession victim. The sweetest moment of all this season is when they meet Charlie. Since they lost a child and she lost her parents the three of them have a really cute moment and both find some closure finally in their lives. Kevin is also introduced and Castiel & Crowley both return to help the couple finish off the leviathan. Working together they barely all make it through but in the end the husband stabs the leader and gets sucked into Purgatory, ending the season.