The 9/25/2008 Washington Post had a banner for NASA's 50th anniversary. The banner asks: "Where do we go now?"
My modest suggestion ... how about: past low Earth orbit?
And since, sadly, NASA must reacquire the ability to leave LEO, a shorter-term goal. How about: not retiring the shuttle until there's something to replace it?
That is: let's not be so lame that NASA must buy rides from the Russians to reach the space station largely built by NASA itself. Meeting this latter goal requires only the political will -- in the White House and Congress -- to maintain the shuttles a few years longer.
You wouldn't think these answers were rocket science.