I am heartbroken over the end of this era.
There will still be manned space flight, and American astronauts will still be involved in the ISS project, but we will be dependent on hitching rides with the Russians and Europeans.
I teach high school science, and I always take the time to tell my students about shuttle launches. It is still mind-boggling to me that people climb to the top of the shuttles, strap in, and basically get blown off the face of the earth.
That said, I think that retiring the shuttles is the right thing to do. We, as human beings, are at a point in space research where we can collect and analyze massive amounts of data from telescopes, remote sensors, and space probes. All of the current research on exoplanets, dark matter, and the history/fate of the universe involves remote sensing. And let's face it, it's hard to justify spending money on manned space flight when unemployment and underemployment are so high.
One ongoing project that I find absolutely fascinating is the European Space Agency's Mars500 "mission." Mars500 official site Sending a manned mission to Mars would entail locking 3 to 6 people into a confined space for years. YEARS! I mean, think about a 3 day family road trip, and then think about it lasting years. Psychology becomes a significant issue. The Mars500 mission is an on-Earth simulation, complete with built-in communication delays of up to 15 minutes. There have been other simulation attempts, but none have been successful. It will be interesting to see how this one turns out!
(a moment of silence for the American shuttle program)