Best Practices/Thinking Ahead

I’m about to set up a WPMU-based system that I expect to grow from a few dozen to a couple thousand sites over a period of 12-24 months. In the end I expect to peak at 4-5 thousand sites, maybe 50% actively updated, but that will take longer than 24 months.

Anyway, I’m trying to think ahead and come up with a plan that will be future-proof but not be exceptionally expensive right now. Anyone have thoughts about best practices here? What would you have done “right” if you started over? I’m thinking about using a dedicated server right now as the web and database server, and then add additional database machines as needed—but I’ve also considered using cloud hosting for easy additional database servers. What do y’all think?