I'm 3/4 of the way through the book - all that's left is Part 2 of Luisa Rey, Robert Frobischer, and Adam Ewing. As noted here or in the Blu-ray software thread, in the book you read the first halves of each of the six stories, and then finish them by reading the second halves in reverse order.
The Wachowskis seem to have added more connections between the characters from story to story than were in the book, and that's not a bad thing.
Sloosha's Crossin' an' Ev'rythin' After had some major changes in the movie, as did An Orison of Sonmi~451, but I think the changes worked, esp. re: speeding up the pace of the Sonmi story, though it changed the twist in the story and left out the part re: the millions of Ascended Fabricants, I believe.
The Ghastly Ordeal of Timothy Cavendish had less major changes in the movie than these.
Having read only the first halves of the following, I don't recall many significant changes in the movie:
The Pacific Journal of Adam Ewing
Letters from Zedelghem
Half-Lives: The First Luisa Rey Mystery
Many have said that Cloud Atlas was an unfilmable novel, but based on what I've read so far, I think the Wachowskis did a great job.
Edit: Just finished the second part of Half-Lives: The First Luisa Rey Mystery. For this story the movie overall follows the book, but also makes some significant changes, more than were done with the Timothy Cavendish story.
Edit2: Just finished the second part of Letters from Zedelghem. The movie cuts out some characters, but is otherwise fairly close to the book, though in the movie I don't recall any mention that Vyvyan Ayrs had syphilis.
Edit3: Finished the book. The Adam Ewing story sticks fairly close to the book, but there are some significant changes as well, which I liked.
Edited by eweiss - 6/25/13 at 7:51am