It would be a clever hack to monkeypatch urllib2.HTTPHandler to override requests to certain hosts and instead send them to in-process WSGI applications. That would mean that any urllib2-using Python app should be able to work this way, including Twill or whatever else.
That's what I meant, but no "monkeypatch" is required: you just use a different handler instead of urllib2.HTTPHandler.
...oh, see what you mean -- it's the "persuade twill (or whatever) to use it" part that's troublesome. Sorry for spamming your blog so much ;-)