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At Digg we had probably a hundred or so tables, each table had varying indexes (a char here, an integer there, a date+time here)

This may be part of the problem, actually. 100 tables to serve posts with attached comments? Um.

There's a bit more going on there. See http://www.codinghorror.com/blog/2009/07/code-its-trivial.ht... for a related principle.

True, but I can't imagine more than a couple of those tables are accessed at the high frequency rate that requires performance optimization.

Actually, my thinking was 100 tables... so what! That's not a large number. Any software of average complexity will have 100 tables, easy.