1. Add these lines to your .bashrc (or other shell rc) file:
alias rmpyc='find . -type f -name "*.pyc" -print -delete' export PYTHONDONTWRITEBYTECODE=true
The first part gives you a handy rmpyc command to recursively delete .pyc files.
The second part tells Python not to write .pyc files anymore.
2. Source your rc file and run rmpyc from your home directory (on UNIX, from ~). This will delete all the Python bytecode from your home dir onward. You don't need to keep it around because it'll just get rewritten as needed anyway.
3. Delete the virtualenvs that you're not using. (e.g. if you use virtualenvwrapper, delete the directories in ~/.virtualenvs/ that you don't need).
4. If you use VirtualBox, delete the virtual machines that you don't need.
5. Delete the repos that you don't need around anymore.
In my case I freed up 3 GB by removing the .pyc files and 25 GB by removing the virtual machines. I forgot to check how much space my unused virtualenvs took up, but it was probably a non-trivial amount.
My numbers are probably higher than most because my laptop's almost 5 years old and I mess around with random Python packages a lot, but you should still be able to save some space. At the very least, it'll be like squeezing the last paste out of a toothpaste tube.
Note: originally the instructions said the following, but I updated them after advice from Dan Crosta, Glyph, and Kit. Thank you all so much for the tips!
alias rmpyc='find . -type f -name "*.pyc" -print0 | xargs -0 rm -v'