It seems like being single-file is mostly gimmick. What are the drawbacks to creating a folder with an __init__.py and a handful of readably-long files?
I haven't used bottle yet (just starting), but I'm very impressed with the templating code which seems very powerful and simple. Including the templating system along with the rest of the framework in a single file, forced the developer to think about it more.
See also the SQLite amalgamation for another example of a single-file deployment: http://www.sqlite.org/amalgamation.html