How can I optimize use of Civilization III in VirtualBox?
Tuning performance on one system stacked that deeply with layers of software is tricky - you will need to observe and measure:


The game performing against Windows 7 so that you could see if Windows needs settings changes to run the game more effectively.
The Windows OS running against the VirtualBox environment and seeing if VB settings can make windows run better.
The Virtual Box runs on OS X and you'll need to see what OS settings might influence how well that runs.


Since we're an Apple centric site, I'll get you started on item 3 on how to measure things on the OS level open activity monitor when you are running things and get a sense whether memory, disk or CPU is being stressed. Hopefully it's just one of the three items and you can then see if tuning and optimizing for that one area helps your gameplay more satisfying.