The HD 650 doesn't have flat impedance, but it's not a demanding or difficult load by any means.
This isn't magic. I own the E5 and the HD 650. For nearly everything -- all my music -- the E5 provides plenty of power across the spectrum. Even at the point where I can't take it any louder, both still perform together.
But I have some bothersome DVD rips I've made that are just too quiet. Never mind bass or mid-bass or treble or synergy. The E5 can hardly make the vocals audible even if the player's volume is set to 99. With the M-Stage at 0dB gain, it's the same thing. If I set the M-S' gain to 18dB, I can set its volume to 50% and it works. Then music is deafening unless I reduce the volume drastically but that's the way it goes with gain.
Does the E5 work well with the HD 650? Yes, very well ... within the E5's limits.