The Most Powerful Villain Dean And Sam Have Fought On Supernatural
Supernatural operates with a pretty specific formula. The Winchester brothers, Sam (Jared Padalecki) and Dean (Jensen Ackles) confront a terrible evil, fail repeatedly to defeat it, go on a quest to become capital-S Stronger, then at last have an all-out battle and topple their foe. Wash, rinse, repeat with ever more powerful antagonists and ever-heightened stakes attached.
We're not besmirching this format, goofy though it may be. There's a reason Supernatural lasted an astounding fifteen seasons, and why we keep telling stories that follow this basic format all over the world. One person's trash, after all, is another's treasure — and if Supernatural is trashy serial TV, then it's very, very fun trash of the sort that is welcome on our screens any day. Not everything has to be discerning prestige television with lush sets and meticulously-researched period costumes; watching Dean put a shotgun to the neck of some acid-spitting creature and pulling the trigger with a cheesy quip can be pretty damn satisfying television, too.
Due to its traditional storytelling format, Sam and Dean have tussled with a number of powerful beings of all objective moral affiliations as either primary villains or secondary antagonists. They have crossed paths with archangels, various demons in Hell's hierarchy, an army of monsters, and straight-up Satan — but of these enemies featured in Sam and Dean's endless travails, who comes out on top as the most powerful?
Sam and Dean's arms aren't too short to box with God
Well, it's pretty tough to beat out God, right? There's the whole created-the-universe thing, plus the fact that he can blow up a being as powerful as an archangel with a mere glance. Sure, an argument can be made for Amara (also known as The Darkness), a primordial being of near-limitless power who is supposedly even older than God Himself — but Amara has never had the same level of personal investment in Sam and Dean as Chuck Shurley (as God is wont to call himself in the Supernatural universe) does.
In their conflict with Amara, the boys simply kicked a hornet's nest; once that feud was settled, she became content to return to existence as usual. Plus, Amara's conflicts with the Winchesters only go back a few seasons; Chuck has been engaged in a cold war of accidental subterfuge with them for ten years, though the boys did not know it. Fans of the show debated whether Chuck was actually God for just as long, with little confirmation until relatively recently. You can argue over whether Chuck shifting from being a mere prophet to being the actual, Abrahamic God is a retcon of convenience by the showrunners based on insistent fan theory, but at the end of the day, none of the Winchesters' foes have been as powerful and as determined to bring pain down upon them as God Himself.
Setting aside the (very amusing) jokes about how Team Free Will's job in Supernatural's fifteenth and final season is to literally fight God like they're in a dingy Lawrence dive bar, it's a profound thematic statement that the most powerful foe in Supernatural is an avatar of fate. Chuck has insisted from the beginning on telling his specific story, and the boys duck it at every turn, even before the actual character of Chuck was introduced on the show. There's nothing more powerful than the ability of manifest creation, and yet even that level of power still often falls flat when the Winchesters are on their game. Free will, indeed.