Any book would be a good start. I guess the Horus Heresy novels would be the first chronologically in the universe's timeline but I've heard people mention that it is better to have a bit of knowledge of the universe as it makes it more enjoyable.
My first foray into the novels was the Eisenhorn omnibus and it is a great read. My main exposure was the Dawn of War games and some minor reading up on the universe online inspired by the games (universe history, Horus Heresy, the Emperor, the creation of the Space Marines, stuff like that). I didn't find it hard to get into the universe and I've read half a dozen more novels since, Ultramarines omnibus, the first of Gaunt's Ghosts omnibuses: Foundation, so I haven't read a lot but I have enjoyed what I have read.
It also depends on what interests you. Do you want to read primarily from the view of the Space Marines? The Imperial Guard? The Inquisition? Chaos?