I'm also having terrible issues with Akismet letting spam through - Approx 5/hr for my higher traffic blog, and a dozen a day for the low-traffic ones I manage.
I reinstalled Akismet, double-checked my API key was still valid, etc on my main blog, but still no success in stopping the spam. It also doesn't seem to be version specific, since the blogs vary from the late 1.* versions to latest 2.1 of WP, and Akismet versions also vary accordingly.
And it isn't clever spam either, it's casinos, britney nude, medication, all the most obvious stuff.
Is it possible that the Akismet filter itself is being too lenient and letting junk through for everyone?