I recently met Mario Wolczko who worked on the Self language, and
asked him if he had one sentence of advice for Python. His response
was: Just-in-time compilation.
About psyco: I think it's wonderful. But, you are right, nobody is
using it. Why? Simple: It's not 'on' by default.
I don't think that's the real reason. Last week Jimmy Retzlaff gave a
talk at the Bay Piggies meeting on optimization, using a large
commercial application he's written as an example. He mentioned that
he had tried to use Psyco, and that it had been turned on in some
distributions of the code, but that it was currently turned off again.
I don't recall the reason he stated for that, but I suspect that it
was mostly Psyco's memory bloat, plus the fact that his code was "fast
enough" and he was able to code things in C if needed. (He also
showed a nice anecdote about Psyco being faster than his hand-coded
C in one case, but that didn't last long when he realized the C code
was using doubles and the Python code was using ints. :-)