So they sat out to move from Postgres to MySQL and completed that just the yesr before I was asked to look into performance and scaling.
They were running on 32-bit kernels on 64-bit machines, using MySQL 4 with MyISAM, using 1 or 2 HDD per machine.
There were a few easy wins – move to 5.0, move to 64-bit kernel, move to disk arrays, use thin wide stripes.
Use memory tables for GeoIP and other busy, static tables.