Almost all the awkward modules I've come across work when you use --system-site-packages

Which ones? You can get some help. Learning virtualenv is a smart long-term move

This. We've all wrestled with problem modules. Qt comes to mind for me. StackOverflow has always been helpful I've never seriously considered ditching venv.

If you're on a Mac, good luck getting pip to install mysql-python. I use Macports for that.

This isn't a good solution. I pip install mysql-python several times a week on my mac ( I use different venv's for different branches and we have several different services that I work on in a given week, thus I'm installing packages via pip A LOT) and we always install it in a venv. Sure it can be a bit of a pain but it's well worth it IMO.

Our steps to always get it working: make sure mysql_config is in your path env variable, make sure the xcode command line tools are probably installed, and make sure the mysql command line client is setup and working correctly locally. Past that is just works for us on Mac OS X 10.7+. I think 10.6 and earlier also work but I'm not sure.

I couldn't ever get it to compile, but I haven't tried in a while. I don't actually need it much these days as I'm using Postgres for most things.

I'm sure there are other packages that are similar: not so easy to get working with pip but not impossible.

That I can remember, yep, PyQT and PySide, and Psycopg. Psycopg is not a problem on Linux, only Windows.