I should add that this conversation is about the Opa platform (http://opalang.org). The feedback we are currently gathering from the community is going to play an extremely important role in shaping the future of Opa.
If your having several instances load-balanced, you can easily update your site, one instance after another. No server runs mono-process. What do you think?
There's no easy answer to your question. Although Opa raises warnings when it detects that the databases your accessing/trying to modify have changed, I guess you'd have to think of a migration process anyway.
What is your best practice so far? (and your expectations :p)