I feel inclined to include some SF novels by Harry Harrison or Arthur C. Clarke, but the first real, honest-to-gosh, definitely-aimed-at-grownups novel I remember reading all the way through was probably Stephen King and Peter Straub's fantasy/horror epic (and honorary Dark Tower story) The Talisman, which was also the first really long novel I ever finished (I'd struggled with both Fellowship of the Ring and Dune the year before).

I really wasn't much of a big reader —outside of the usual media stuff— for another couple of years, but this was the one that really got me into genre lit.