When Metatron reads the new ending of Chuck's story, he looks crushed. Look at this sad little face. And as we see this, Chuck is singing "one of these days, I'll be gone." So, is Chuck planning to sacrifice himself in order to put Amara away? (Theory 1)
Damn you, Curtis Armstrong. How dare you make me have feelings for this awful, awful character.
And speaking of sad, Chuck seems very sad when he tells Metatron that Lucifer wasn't his favorite, but also that he wasn't a villain. I feel like this has to be important. Are they setting us up to accept Lucifer as a hero, who will sacrifice himself (probably being tossed into the Empty) to put Amara away? (Theory 2) Maybe with Sam's help, as per my speculation earlier? (Theory 3)
More sadness? How about Sam telling Dean "We're not gonna make it; we were never gonna make it." Did the fog actually implant negative thoughts into its victim's brains, or did it only bring out the worst thoughts they already came up with on their own? Because if it's B, and I think it is, it means poor Sam is always carrying those thoughts with him, and tamping them down.
Let's end on a happy note. Sam tells Dean to "quit ironing my shirts with beer." That means Dean irons Sam's shirts on a regular basis. I love this so much, I'm just gonna roll around in it for a while.
(And, a reminder, no spoilers in the comments please!)