After all my tinkering trying to get things to work, it seems to me like it is one of a few unique issues:
1) there are certain chipsets DDO doesn't run well with
2) DDO doesn't play very nicely with AMD CPUs
3) DDO doesn't play very nicely with AMD FX CPUs (my guess is this is the real culprit)
4) some combination of the above

I think it has something to do with the AMD FX CPUs in particular, because if it was AMD CPUs overall you'd see a lot more people complaining. Though I guess it could be a combination of certain chipsets and AMD FX CPUs. The board I had was a Gigabyte GA-78LMT-USB3. I switched over to an Intel setup with the same GPU and now I get 4-10x the framerate I did before. My board now is a Gigabyte GA-Z170N-WIFI.