There are too many to mention, but here are a few of the biggies:
The book took place in the 1950's; the movie in the present (mid 1990's-early 2000's) day. [Originally they had picked the date 1996, but later decided to not be specific about it.] The book had a frame story where Landon tells us the story of how his life was changed back when he was 17. The first draft of the screenplay kept the frame and had Landon visit the Reverend Sullivan 35 years after Jamie's death and return the wedding ring because he had met someone new. The first part was deleted and was changed to the coda in the movie where he returns only 4 years later, having achieved his goals (getting out of Beaufort, graduating college, getting into med school), and returns the book that Jamie gave him to her father. These changes were made to add sympathy to London's character. It was felt -- and rightly so -- that the audience would react negatively to the movie starting out the original way. These changes were made after they began filming. The shooting draft still had the frame story. In the book Landon got the lead in the Sunday school Christmas play. In the movie it was the high school spring musical. [It's interesting to note that while they completely replaced the play in the movie, the lead character Tom Thornton remained the same.] Landon's friends were changed quite a bit in the script (and later on stage by the actors). The only noticeable similarity was that his best friend was still named Eric. In the book, Landon was the ring leader of his friends (sort of; that's how Sparks describes it in the DVD commentary, but I got the impression that Eric was the real leader). In the movie this role was given to Dean to create an adversary for Landon. In the book Jamie was much sicker at the wedding than she was in the final version of the film. In fact, this was included in the early cut of the film, but these things were cut out by the director because he felt that the second half of the film was depressing enough. Hegbert [Rev. Sullivan]  was more developed, and much older in the book The circumstances of Jamie's mother's death were explained in the book (and in the script, but the scene was deleted). She is only mentioned once in the finished movie, where Hegbert and Jamie are talking in the hospital.
Nicholas Sparks explained some of the changes with the following on his website:
One thing that I'd like you to remember [when seeing the movie] is that the movie will be different from the book. It has to be, not only because films and novels are different mediums and do things different ways, but also because every single reader saw the movie in their own mind and it's impossible to match everyone's imagination. But please, see the film anyway. It stars Mandy Moore (Jamie), Shane West (Landon), Peter Coyote (Hegbert) and Darryl Hannah (Landon's mother), and they all did a fabulous job.
As for specific differences between the novel and the film, I'd like to touch on those briefly.
First, the film is set in the 1990s, not the 1950s. This was done because both the producer and I thought this was such a wonderful film for teenagers because of the message it provided (strong faith, kindness, forgiveness, charity, redemption, looking past the obvious to see the person within), especially compared with most movies geared for teens these days. A simple fact of Hollywood is that if we'd set the film in the 1950s, teens wouldn't have gone to see it. To interest them, we had to make the story more contemporary. Secondly, the play was changed. I won't go into details, but it's not the Christmas Play. The reason for that was because the Christmas Play was Hegbert's way of showing that he'd once struggled as a father and the struggle was difficult to overcome. Yet, due to time constraints in the movie, this involved a sub-plot that simply couldn't be worked into the story. People who'd read the book would understand it, but people who hadn't read the book would question whether Hegbert was a good father. Because he is a good father and we didn't want that question to linger, we changed the play. Thus, the end result for Hegbert is the same, it was just handled differently. And finally, the things that teen boys did in the 1950s to be considered a little 'rough' are different than what teen boys in the 1990s do to be considered 'rough.' Landon's a little rougher in the beginning of the film, but his redemption is that much greater by the end. In my mind, that was a fair trade.