Python is a joke. Semantically, you're put in a straightjacket1 (thanks, Guido!), and tuning for performance is impossible2.
Either use a powerful high-level language (Common Lisp) or go to back to C. You might say, "but I'll mess things up in C." But this is exactly the point! If we remove all of the lame languages that let total failures write code, they will have nowhere to go, and the Order will be restored once again.
In general, remember that when you use a language above native machine instructions3, you're accepting the abstractions and philosophies of the people who created that language. If you have to use something that's broken or backwards just to stay afloat (or worse, you don't realize that it's broken or backwards), something is wrong with you.
1 Before you tell me that "it supports functional, LOL!": no, it doesn't. Obviously, very few people can define "functional" precisely, but if you take 10 minutes to do a little Googling, you'll find that the functional features of Python were crippled from the start, and Guido has expressed specific dislike of even those. It seems like Guido would prefer to make his language "idiot friendly", rather than powerful, in order to get a large number of people using it. It's not just functional programming either. Everything in Python reeks of the "one correct way to do it", to the point where doing anything complicated feels tedious.
2 Obviously, a better data structure or algorithm will always help, and often people who complain about performance don't know what they're doing. However, doing anything beyond that in Python is basically impossible, save for some of the projects like Psyco (which sort of work sometimes, but not really), or writing your core functions in C and then interacting with them in Python. The last time I tried the latter, it was downright fugly. Contrast this with Common Lisp (SBCL), and a person has a valid reason to find the state of Python unacceptable.
3 I realize that you can "pick" different architectures, and could theoretically create your own. But since the former is limited to a handful of choices, and the latter basically never happens, I decided machine instructions were a fair choice for the "unmovable bottom" of the hierarchy.