Lonesome Dove - Larry McMurtry

This epic tale of the West won the Pulitzer Prize in 1986.  It is a sweeping drama of rugged western life, human ambition, injustice, poverty, struggle, redemption, love, joy, and relationships.  All of this heavy material is joyfully lightened by the outstanding wit McMurtry wields through the wry main character: Gus McCrae.
Two retired Texas Rangers decide to form the first cattle ranch in Montana.  The novel is the story of their journey northward and all the people this journey involves.  McMurtry beautifully sidesteps the plot to develop each main character's backstory in full-chapter flashbacks.  This rich character development weaves a thick fabric of intense human drama for the subsequent plot developments.

At first I thought the theme was the ultimate poison of ambition.  As in: ambition will destroy everyone around it.
Then, it had no theme.  I thought it was simply an outstanding story depicting the beauty, danger, and difficulty of the old American west and the humans who lived there.
Finally, today, with some help from wikipedia, I picked up on what I think is the true theme, cleverly disguised in a mangled latin phrase on an old wooden sign in the story: "We are changed by the lives around us."  For the many, many intriguing characters who inhabit this story, life has surprising ways of wrapping back around on itself.  Our actions influence those around us.  Our stories intertwine.  Both our good choices and our bad choices make a difference for those we love, and even for those we barely know.
That's a message worth a good story, and all the better if the story itself is exceptional.  At some point, I want to go back and watch the TV miniseries again, too.