I'm working on (yet another) Django upgrade for a client and the project is old enough that it's affected by the structure changes in Django 1.4, compounded by some seriously custom structure of its own. I kept getting an error from Django's autoreload saying The system cannot find the file specified: 'manage.py'. I traced it back to the prefixes on ROOT_URLCONF and WSGI_APPLICATION in the settings and then some path manipulation in the wsgi file, but along the way I suspected there might be some hard-coded paths hidden in __init__.py files throughout the app and managed to find all of the possible candidates with find . -name "__init__.py" -size +1c.
Oh yeah: and always delete .pyc files when your changes don't seem to have any effect!