Hi guys... This is one of the first bits of good luck or good news I've had with dnn so far, so I definitely figured I should let you know...
I did a completely clean install (again) of version 5.1 and then rebuilt one of the Portals from the ground-up again... Very time consuming, but at least it was still relatively new. Speed was still horrible on both the old and the new installations, but I created separate application pools for each instance of dnn on the server. This solved the speed issue with the new (5.1) installation immediately and almost completely.
Obviously this isn't a fix for everyone, but perhaps that will help.
I did also try all the Caching and Compression settings with pretty minimal noticeable changes.
The bigger problem, it turned out, was that a piece of one of our purchased custom modules was running up the server resources b/c of how it was attempting to use 404 errors. Once that piece of code was removed, the old Portal (with the modified Cache and Compression) settings started to fllllyyyy.
My new Portal is still much slower than when I wrote this out as a custom CMS system, but it is DEFINITELY much much better than it was and at least people can use it now! :)
I'm still losing Session state quite frequently and am still working on a hack to keep that going.
Thanks for the ideas in this thread... I guess my only contribution is to, if possible, give your dnn applications their own Application Pool on the server.