<p>When starting a new ASP.NET application, with the knowledge that at some point in the future it must scale, what are the most important design decisions that will allow future scalability without wholsesale refactoring?</p>

My Top three decisions are
Disabling or storing session state
in a database.
Storing as little as possible in session state.
Good N-Tier Architecture. Separating business logic and using Webservices instead of directly accessing DLL's ensures that you can scale out both the business layer as well as the presentation layer. Your database will likely be able to handle anything you throw at it although you can probably cluster that too if needed.
You could also look at partitioning data in the database too.
I have to admit though I do this regardless of whether the site has to scale or not.