The Shuttle has been an amazing achievement and a splendidly capable piece of machinery. And, once the orbiter shed the ungainly solid boosters and utilitarian external tank, a beautiful one.
It has also been, like the Concorde, an economic disappointment that attempted too much too soon and promised too much, a costly detour on the road to growing human use of the universe beyond our atmosphere. The magnificent yet fragile machine has been described as a hypersonic Ming vase.
Keith Cowing has written a moving reflection on the program . Rand Simberg describes 6 False Lessons of the Space Shuttle, and he's mostly right.
I'd argue with his #3. The Shuttle Proved that Cargo and Passengers Should Travel on Different Vehicles. At the current state of the art, we want a manned spacecraft using a launcher that's as simple as possible (to minimize failure modes) that flies as often as possible (to build reliability). In practice, that means a fairly small manned spacecraft with very limited cargo capability.
He also argues here, that the last flight of the Shuttle only marks the end of the big government model for the best way for humans to flourish beyond our atmosphere.
I hope that he's right.