Yes.

It is stressful.

Look for libraries that make working with WSGI as painless as possible. Working with WSGI directly allows you to write modular code that works together gracefully with other WSGI code. Pylons is really just an amalgamation of WSGI modules. Smart people can amalgamate their own modules.

Django was written before WSGI was an established standard. It has the advantages of being established, a relatively large pool of developers, and the admin interface. It has the disadvantage of dictating your project layout, not integrating well with other WSGI modules, and having a large degree of lock-in.

The best options are Flask (for a simple start), Pylons (for more obvious out of the box functionality), WebOb (for a simple and slightly too magical WSGI library), and Werkzeug (for a well-written library that dictates nothing).

My ill informed opinion: the WSGI specification (i.e., PEP 333) together with a decade or so of cross-pollination seems to have made most Python web frameworks more similar than different. You can opt for more out of the box functionality at the expense of less flexibility, but not much else. (The exceptions seem to be where the code is really old and/or asynchronous.) Django seems to be the BDFL blessed option.

Example: Everyone seems to think that Google copied "their" Python web framework in creating the "webapp" framework for App Engine. webpy, Django, ...

The April Fools python micro-framework was called 'Denied.' The Hacker News coverage is here, http://news.ycombinator.com/item?id=1237412 .