The Darkness, Amara, aka God's sister was released when they removed the Mark of Cain from Dean. The boys had a whole 'nother problem on their hands, bigger than any other they've faced before.

"Believe me Cas, your family tree's a damn cactus." Dean clenched his jaw. "Cause you're all just a bunch o' pricks."

"Yeah well if we don't think of something quick it's gonna get worse." Sam mentioned. "Any ideas, Cas?"

"This is not just another matter with demons or angels." Castiel shook his head. "Amara... she's not gonna be an easy target."

"You think?!" Dean scoffed.