This is a tough question, with an element of “answers may vary,” because every book faces slightly different challenges. I often struggle with figuring out WHAT exactly pushes the characters apart and how I can make it EVEN WORSE as the story progresses. If I get that nailed down, the ending can give me trouble. Not the “how do I solve this” part of the ending, but the “how do we say good-bye to these characters so we know they’ll be endlessly happy” part of the ending.
In revisions, the book fares best if I go over and over it, with several weeks down time between layers of varnish. The downside of that approach is that I get tired of the book, even as each review cycle reveals more to polish. This can produce anxiety, and buffing a book this way can take a long time.
If I had to put a finger on one aspect of writing for publication that’s most difficult, it’s that I must let the book go. Once the book is published, particularly if it’s traditionally published, it must stand or fall on whatever merits it had when it left my hands. If I wake up a week later with my head full of snappier dialogue, more imaginative settings, and cleverer symbolism (and I do), that’s too bad. The book has been released into the wild, and belongs to the readers now.
Letting go is so hard, that the only way I’ve found to deal with it, is to write another book.