In my experience, six was a relatively minor part, and you could get by with your own little compat file for just the stuff you needed, even on relatively big projects. I even found it beneficial to do so because instead of just slapping six.moves everywhere you'd have to re-evaluate some of the old decisions (e.g. at $dayjob at the time we were using all of urllib, urllib2, and requests for HTTP calls, not using six provided strong motivation to just move everything to requests). This also made for a lot less churn when removing Python 2 compatibility.