Orson Scott Card's Ender Quartet

This is a magnificent science fiction saga, consisting of the refreshing, surprising and thrilling "Ender's Game", the masterful "Speaker for the Dead", the cerebral and somewhat contrived "Xenocide" and the inevitably underwhelming conclusion, "Children of the Mind".

Card deals with ethical issues constantly in this series, not as an after-thought or a side-thread, but as the main theme. The science is not the focus, and at times it's not even very credible, but that doesn't affect the soul of the story. There is a lot of spiritual under-current in this story as well (a bit too much for my taste).

This might quite possibly become the reference manual for humankind when we eventually run into extra-terrestrials, just like Clarke's works were for the Apollo mission.