Can it be done? Yes: checkout
Both sites use the same ACS4.2 install. Both use mostly the same set of scripts, but separate template (.adp) directories. Actually they even share a lot of adp files, but with different configurations based on the domain name. This involves quite a lot of hacking on top of acs, and a few changes to the templating system.
For a number of small sites on one OACS4.5b1, only one using OACS, checkout:
These sites use my Virtual Abstract Templating module. Caffeumbria is using the templating part at
http://caffeumbria.com/blends/.
The VAT module is available from http://zmbh.com/vat/
One thing that was possible in the 3.x series of OACS was to use separate database pools per server with my module. This is because my module would set the server parameter, and pools in ACS are pulled from [ns/server/$server/db] and ACS parameters are pulled from [ns/server/$server/acs]. I have not checked it this is still possible in 4.5, probably it is not.
