Amazingly, the reviews of the movie Cloud Atlas manage to identify the two most substantial problems with the book itself. Instead of identifying them as such, however, they attribute them to problems with the movie (e.g.). These two problems are:
1. The genre "mash-up" that involves taking stock plots and doing little to enliven them (a robot develops the feelings of a human; a postapocalyptic wasteland that's much more like primitive nature, etc).
2. The vague quasi-spiritual transcendental nonsense which is mostly hinted at in the book.
The problem with the movie is that it forces this content to become literal, and when it is literal, rather than implied, it comes across as banal or insipid (or camp). This is not because the movie is a failure: it's a problem with the source material: the plots really are stock genre plots with little to enliven them; Mitchell conspicuously avoids saying anything concrete about the spiritual consequences of the overlapping plots: you might think this is skillful omission requiring the reader to draw their own conclusions, but you might just as easily think it's because there isn't any unified, satisfying explanation of it.
What this gets us to is the problem with the cult of style in contemporary literature. It's possible to write beautiful sentences that never actually say anything useful or interesting, and this, it seems to me, is Mitchell's problem. Readers get caught up in the sentences--in the feeling of reading the book--and never really wonder about what the book itself is about. Readers think that something technically difficult--writing across different genres--is impressive quite apart from the strength of those individual units (it puts me in mind of the praise for Louie, which seems at least as much to derive from nothing more than the sheer fact of his writing comedy and drama, or Socrates' observation in the Republic that artists go astray when they attempt to work in more than one rhetorical mode), and the fact of having completed the book somehow compensates for this. But surely it also matters what a book says, and this, I think, is much less commented upon, so much the worse for our aesthetic tastes.