I'll keep it spoiler-free at the risk of being vague.
I recommend going into Cloud Atlas without knowing too much about Cloud Atlas. If you're already familiar with the novel's structure, then Mitchell's repeated, explicit attempts to bash the concept into your skull will be tedious. Nonetheless, there is a beauty to some of the more subtle and nuanced connections between the stories. I don't mean to bash the book with my two-star rating, as I do genuinely believe, in accordance with Goodreads rating guidelines, that “it was ok.”
There is a lot to chew on in Cloud Atlas: religion, immortality, oppression, discrimination, capitalism, metaphysics, and more. (Mitchell has some genuinely interesting ideas about some of these topics.) Plato, Nietzsche, Freud, and Solzhenitsyn are all there too, in addition to other thinkers whose influence I am perhaps too ignorant to notice. It's debatable whether the heavy thematic concepts are a good match for the pulpy or comedic tones of certain sections, but that might be a matter of personal preference. (In different ways Mitchell seems to paradoxically take his concept both too seriously and not seriously enough.) In contrast with my desire for greater subtlety in other aspects of the work, I wish that some examples of prejudice within Cloud Atlas had received more explicit challenges. While the characters' racism is generally addressed, some men in the story express a misogynistic sentiment that in my view Mitchell doesn't adequately explore, in my opinion.
A flawed work for sure, but at least a thought-provoking one. If this “genre” of interconnected storytelling had more time to mature, I wager that it could be a vehicle for some genuine masterworks, but the pool of writers capable of writing in such different styles as Mitchell does is probably rather small. Frustrating in some respects, and not a life-changing work of literature (at least not for me). Perhaps my expectations were too high, but it's a book that has stuck in my mind, and that has to count for something.