I am quite sure that the Basecamp cluster contains tens of machines. It also features a rather clever caching design. Please don't try to justify a push towards simplicity as lack of ability to handle complexity.
A) I don't subscribe to the idea that building guis on data stores is in any way demeaning and/or easier than other kinds of development work.
B) I do think that if that is the main kind of systems you write (and I could be mistaken but all of 37signals products look like that to me) it will impact on your design philosophies and your thinking about quality assurance in ways different than other sorts of systems.
The requirements are completely different for a system that is taking info from a user, persisting, and giving it back to them later, than for a system that is processing information and acting on it.
Those different requirements will drive different architectures and different QA processes. None of that means you can't document those requirements as automated tests at the beginning of your coding cycle.
