How far does the power of God extend in the world of Supernatural, and what precious few weaknesses is he burdened with? Even going back to the Eric Kripke era, God has been a presence on Supernatural in some form. Initially, it was thought that God had abandoned Heaven and Earth without explanation, but when Castiel was mysteriously revived and the Winchesters saved by a higher power, it was clear that God had at least one eye on his creation. The universe's Lord and Savior was then revealed to be none other than Chuck Shirley, the socially-awkward prophet/writer who had been turning Sam and Dean's adventures into bad fiction.
Chuck claimed that he hadn't maliciously abandoned his people, he simply became disillusioned and yearned for a simpler life, even taking time to help the Winchesters deal with The Darkness. However, when Chuck returned at the end of Supernatural season 14, the full truth of his nature emerged. God revealed himself as a true villain, bearing no empathy or care for the life he created, instead wanting to write his "story" using Sam and Dean Winchester as main characters. Having come to the end of his tale, God's desired conclusion is to watch Sam and Dean destroy each other, and he'll sacrifice anything in order to achieve that final chapter, going so far as to trigger the end of the world in frustration.
Naturally, God (along with his sister, Amara) is one of the most powerful beings seen in Supernatural, capable of creating new realities and destroying them at will. Interestingly, the destruction part seems to take a little time, as Sam and Dean were able to prevent the apocalypse triggered in the season 14 finale, and the alternate hipster Winchester brothers had time to escape their universe before God erased it. When playing in the sandbox of his creations, God has virtually limitless power over reality. He can conjure objects out of thin air, blink a person from existence and overpower any opponent with his telekinesis. One of God's most intriguing powers is his ability to change a person's fortune, as seen in season 15 when Chuck removed all of Sam and Dean's luck, causing their car to break down, their stomachs to churn and their punches to miss.
God can manipulate a person's body as he wishes, as seen with Eileen Leahy, and he wields enough power to bring any deceased entity back to life, even from The Empty. Add to that the regular flight and super strength possessed by the angels, and it's easy to see why Chuck is Supernatural's ultimate villain. Arguably God's most useful power, however, is his near-complete omniscience, which makes conspiring against him an extremely tricky task.
But while God might seem all-powerful and impossible to defeat, the character does come with a few select weaknesses, any one of which could be his downfall. In terms of characters who can hurt God, The Darkness is said to be even more powerful than her brother, while Death's scythe is confirmed to be effective against Chuck also. A nephilim has the potential to surpass God's power, although this theory has yet to be proven true in the Supernatural world. God is also prone to hurting himself out of pure arrogance. In season 14, Chuck created the Equalizer gun and handed it over to Sam and Dean, not expecting they would shoot him with it. The resulting bullet wound temporarily wiped out a significant portion of God's power, proving hubris sometimes gets the better of his judgement. There is a spell that can trap God - the same curse used on The Darkness in ages past, but the target needs to be weakened for this to work. The Winchester brothers and Billie have both managed to evade God's ever-watchful eye through trickery.
But God's greatest weakness might just be something he gave to his enemies personally - free will. Chuck's powers allow him to easily kill people, or to force someone else to kill people, but God can't make them want to do it. This limitation is the crux of God's problems in Supernatural season 15, as the villain is a creature driven by ego. Jealousy made God turn against Earth's other divine beings, and a desire to be a "good writer" is stopping him from simply smiting Sam and Dean Winchester where they stand. If God could influence free will, or even just reign in his rampaging ego, he might've been able to avoid whatever grim fate awaits him in Supernatural's upcoming finale.
Supernatural season 15 is currently on hiatus.