For example, Comix uses #!/usr/bin/env python, even when it's installed by the package manager (at least on Ubuntu). This means that if I launch it from a terminal with a virtualenv enabled, then it blows up because chances are that I don't have pygtk on that virtualenv (because I generally don't work on GUI apps). At the very least, things installed by the package manager should point at the interpreter that is under package management.