The basic story (which I'm sure Carlton summarized in his earlier review), revolves around the narrator, John, a rather spineless, uncharismatic kid who, throughout the course of the novel, seems to derive most of his identity from his association with Owen Meany, a strange, short kid with a “ruined voice” and an unshakable faith in the mysterious ways of God.
The book opens with John confessing that he believes in God today because of Owen Meany, and the remainder of the book shows why this is so. It's made up of seven sections (which I hesitate to call chapters because of their length) which are told in chronological order. The book follows John and Owen from elementary school through their late teens.
I mostly enjoyed Prayer. The characters were likable and believable, the plot was interesting, and the religious aspects were all handled very well. My only complaint was that parts of the book, particularly when the older John is speaking, sometimes read like polemics against Ronald Reagan and American foreign policy in general. There's nothing inherently wrong with that, I don't think. After all, an author can write about whatever sentiments he wants, but in context of the entire story, the political asides were a) jarring and b) somewhat dating, since John is supposed to be writing from the present day.
Still, these complaints are fairly minor, and I enjoyed Prayer. I'd like to check out some of Irving's other work, although his books are long enough to make them slightly time prohibitive.