You could run two instances of the Web Server service, both pointing to the same session manager and configured to use the same Relay.

Or you could detect the host header in program code and make the appropriate changes. You may want to just use different resx files. Here is how to do it not based on language:
http://stackoverflow.com...based-on-some-parameter

Or a hack would be just to put each customization in a different "dummy" language and set the language based on host header.

It really depends on how extensive your customizations are.

How about a simple trick:

1. Create a new Folder in SC Folder App_Themes called PortalBrand
2. Create Default.css with contents:

3. Build your branded Site, put an <iframe> in it with URL http://your-sc-url:8040/?Theme=PortalBrand

This way we integrated SC into our Homepage.