I went from a pair of MDR-7506 to the HD650 and a DIY O2 amp (had to buy all of the soldering equipment as well) within about 2 months of spending time on Head-Fi.   I can't imagine how much money I will end up spending on audio in the next few years...

Headfonia also said that the O2 beats the c421 in terms of sound.  If you have no need for portability, I think buying or building an O2 would be the right choice.

I just finished by O2 build a few days ago and am impressed with the sound so far, although I'm waiting for my HD650 to arrive.  Hopefully I'll be blown away.   I'm also thinking about clipping/removing R19 and R23 to get 1x gain instead of 6.5x with the gain switch in.  I'm not sure if 1x...