From your question I am assuming you are evaluating the suitability of E-Smith:
E-Smith 4.0bx supports multiple domain names from the web interface (no command line hacking) here is a quote from the relevant page of the web manager.
> Create, remove, or change virtual domains
>
> When you create a virtual domain, your e-smith server will be
> able to receive email for that domain (provided that the
> correct DNS records are published by your Internet service
> provider) and will also be able to host a web site for that
> domain.
>
> Click here to create a virtual domain.