As always: It depends 😉
When I don’t need any apache features I am going with a pure python webserver like paste etc. Which one exactly depends on your application I guess and can be decided by doing some benchmarks. I always wanted to do some but never came to it. I guess Spawning might have some advantages in using non blocking IO out of the box but I had sometimes problems with it because of the patching it’s doing.
You are always free to put a varnish in front as well of course.
If an Apache is required I am usually going with solution 3 so that I can keep processes separate. You can also more easily move processes to other servers etc. I simply like to keep things separate.
For static files I am using right now a separate server for a project which just serves static images/css/js. I am using lighttpd as webserver which has great performance (in this case I don’t have a varnish in front anymore).
Another useful tool is supervisord for controlling and monitoring these services.
I am additionally using buildout for managing my deployments and development sandboxes (together with virtualenv).