The sentence that stopped me cold in Dune is in the second chapter. Paul has just had his first encounter with a Reverend Mother and she asks him what she calls 'the question that cannot be answered.' He asks what is the question. She says: 'Is that a human being in there?'

The entire novel is contained in that exchange. Arrakis is a question about what human civilization actually is when stripped of abundance. Paul is a question about whether a person can remain human when they become something larger than a person. The spice is a question about whether perception is the same thing as understanding.

Herbert had the entire architecture in place by chapter two and most first-time readers don't notice because they're too busy learning the world. The reread is when you see how deliberate the whole construction was.