I thought this might be of some interest - I have just released a tweaked version of this plugin that will allow a single multisite instance to handle both sub-directory and sub-domain based URLs. Underneath the hood, it uses a sub-directory install but, with a little sunrise.php magic and a couple filters, those sub-directory based sites can be mapped to domain based URLs (or any other). Don't know if it would it be of interest to include in the core of the plugin, but it's available at https://github.com/rorymurphy/wordpress-mu-domain-mapping.
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