My two cents:
I used Blender 2.49 excessively. I liked it the best…
… but 2.56 has blown me away. The older versions had annoyed me with everything from workspace annoyances to the errors in the logic bricks.
However, 2.56 seems to have fixed almost everything I hated, and I love it.
While model editing still needs a little bit work done, it seems much more natural than 2.49.
And then comes the Game Engine, which is a completely different level at 2.56 than 2.49.
What about you? So far, which do you prefer?