Same as any other document on my disk: it doesn't matter. Just dump everything in there and let Spotlight index it.
(That's basically what iTunes does now, except the exact behavior is hidden behind a mysterious "Keep iTunes Media folder organized" checkbox, and the index is stored in big opaque XML files rather than Spotlight.)
My email has hierarchical folders, too, but I don't know anyone who worries about the folder structure of their email. All messages are indexed, and search is quick, so there's not much point.
(That's basically what iTunes does now, except the exact behavior is hidden behind a mysterious "Keep iTunes Media folder organized" checkbox, and the index is stored in big opaque XML files rather than Spotlight.)
My email has hierarchical folders, too, but I don't know anyone who worries about the folder structure of their email. All messages are indexed, and search is quick, so there's not much point.