One thing you'll notice immediately is that our narrator, John, makes himself vulnerable to us from the get-go. Even before we know what his name is, we know some pretty big details about his life: he lost his mother at a young age, and the boy responsible for her death was his best friend, Owen Meany. We also learn that it was because of Owen Meany that John has some pretty deep religious convictions. That highly-personal tone runs throughout the entire novel. (He's even willing to admit to us that he used to have a crush on his own cousin, for crying out loud.)
The other notable aspect of the novel's tone is that it manages to tug at our heartstrings while also making us giggle. It can be really hard to find humor in situations like the ones our characters find themselves in, and yet you'll probably find yourself giggling pretty frequently at all of the situational humor the novel has to offer.