One is the fact that the DBI doco itself IIRC says right in it that the DBI interface is not horribly efficient.

Actually the DBI documentation says the complete opposite. From the FAQ "How fast is the DBI?":

... DBI and DBD::Oracle overheads are small compared with Perl language overheads (and probably database overheads).

This matches my experience. If DBI isn't fast enough your problem is almost certainly IO, hardware or the choice of Perl as the implementation language. DBI was designed for speed - I doubt you'll see much improvement without moving most of your application onto the XS side.

If you've not read it already I'd give Tim's DBI Advanced Talk a look over. It has lots of relevant tips on getting the most from DBI.