To Multi-Database or Not?

The question that I have is when to use the multi-databases?
1. Should I develop the site with all the plug-ins and themes first and then use the multi-database plug-in?
2. If we set up the site with 16 databases, how hard is it to later to upgrade to 256 databases?
3. For hosting we are using a dedicated virtual server at media Temple. Should we stick to the single database until we have reached 5000 sites? and then move to a dedicated server and upgrade to the multi-databases at that point?
4. I am concerned that having multiple databases will be difficult to restore if I screw something up during the site development with the other plug-ins. It is much easier to restore one database, then 16 or 256. What are your thoughts on this?