I've been ABing the HD-600 and HD-650 since my new HD-650 arrived and I'm coming away extremely impressed with both. All listening has been done with an O2+ODAC. When I get a tube amp and a new DAC I'll definitely update my impressions with that as well. I do want to note that the HD-650 was very dark sounding when it first arrived, with significantly rolled off treble and a very bass-heavy sound. During the AB testing right out of the box with my HD-600's there was no contest, the HD-600 was superior because the HD-650 was coloring the sound too much. This worried me a bit, but I believed that perhaps break-in would help and it did. Break-in has made a MASSIVE difference. The break-in on these was anything but subtle. The darkness was markedly reduced within just an hour or two of initial break-in. Several AB comparisons with the HD-600 throughout this initial break-in confirmed my suspicions that the top end was opening up. I actually do recall that my HD-600's did more or less the same thing when I first got them as well. Now the highs are much nicer and are just a bit rolled off and the sub-bass is more pronounced compared to the HD-600.
My initial impressions are that the HD-650 is also a bit more resolving than the HD-600. At first they were not at all, but as they break in the difference has become noticeable. The HD-650 sounds more refined and resolving overall, even though it is not as neutral in its tonality. Once I have maybe 100 hours on them I'll be more certain about my conclusions, but so far I'm loving the HD-650's. Based on my fiancee's initial AB comparisons, she prefers the HD-650 over the HD-600 due to the fact that for her they place the vocals more forward than the HD-600. I think the vocals seem more forward because the treble is rolled off a bit compared with the HD-600. Since she focuses on vocals when she listens to music, she finds this to be a desirable characteristic. I don't think the HD-600's are bad for vocals though, it's just that their neutrality doesn't place them so forward. Before hearing the HD-650's, she still felt that the HD-600's were insanely good headphones (And they are!).
It's important to mention that these headphones have similar "voices" overall. You can tell they are siblings and my belief is that you like the sound of one you will still like the sound of the other. You might PREFER one, but it is unlikely that you'll hear the HD-650 and think it is absolute trash compared to the HD-600 or vice versa. Both are extremely competent and well designed headphones. If you could imagine two people in a choir singing in unison, the HD-600 is just a bit higher pitched and the HD-650 is a bit lower pitched, but they're singing the same song and man is it sweet!
I can't really say which one I prefer, but I'm leaning toward the HD-650 right now. It could just be that they're new though. I like to think I'm not as susceptible to that (Just look at my reaction to the HE-400, lol), but with these it's hard to say because they're similar to my HD-600's. I love the neutral tonality of the HD-600, they just sound so incredibly natural. But I also love the refined, smooth, and yet resolving sound of the HD-650. The HD-650 is certainly natural sounding as well though, it just has a slightly more colored sound. I think the HD-650 is perhaps slightly more musical as well, it seems to get my head bobbing and my toe tapping a bit more. My thoughts on this are that it is due to the more defined low end and forward vocals in the music. I would say that for most people it makes sense to just pick one or the other depending upon your preferences. I don't think you can really go wrong with either at current prices. Luckily for me, my fiancee and I both love the design and sound of the HD-600 and HD-650, so we will be keeping both for sure!
The next step is to get a nice tube amplifier and DAC. I might actually try the HRT Music Streamer DAC after hearing some good things about it.