To succeed in the web framework, Python will need to answer the following challenges:
To be ubiquitious, so that budding developers can find cheap hosting. There has to be sufficient low barriers to entry for the developers as well as the web hoster.
A supported python web framework distribution that can be easily deployed on the hosts. BSD and Linux versions required, with mysql client-libraries bundled. Like it or not, MySQL is still the dominant RBDMS on web hosts.
The web framework must also be easily deployed on Windows hosts, where most incidental developers start from. I believe the initial success of Zope is partly attributed to its availability on Windows.
Sane configuration and deployment story, so that a developer can deploy their tests to the web host consistently, even with different web hosters. This will decrease support costs for hosting companies, and please the developers no end.
(I'd include the configuration of the SQL connection in part of the deployment files).
My vision is that all web hosters which host this framework will automatically provide a user configuration file for this python process that includes mysql connection details automatically. The framework could also do the dirty work of synching between local and remote servers.
There is much we can learn from how Wordpress makes the installation painless.
Changes in python required
Provide a few prebuilt solutions (optional) and pretty templates (important) for solutions to be quickly implemented.
People learn by modifying existing applications. Most people though just want to deploy existing applications.
Can we have the equivalent of PHPBB on Python, or the PhpGalleries, or PhpShop?