I have owned or ridden everything except a CX500C and CX500E
Here's the thing:
Horsepower/Torque- There is no comparison between a CX500/GL500 and a CX650/GL650 engine.
I regularly shock sport bikes with how fast a CX650E can launch off the line, and the CX650C was even faster because of it's power to weight ratio.
CX500 is simply no match.
That being said, a CX500 has a much smoother feel to the powerplant. Engine doesn't feel like it wants to rattle itself apart, even at idle.
Ergonomics- If you are 5'10 or taller, CX650C's suck. They suck ass. They suck worse than ass. They make your ass wish it was dead. After 50 miles on a 650C, Monkey Butt is the least of your problems. Every time I got off of the 650C, I thought my spinal column had decalcified, and my sciatic nerve had a microscopic blowtorch incinerating it from the inside out. The seat (which was basically brand new) sucked, the rear suspension sucked. Ergonomically, Honda seriously screwed the pooch on that bike.
Every other CX or GL I have ridden was ergonomically fine.
(but God, I loved cracking the throttle on that bike)
Gas mileage. If you love cracking the throttle as much as I do, they are surprisingly even.
Maintenance- the CX500/GL500 engine is basically a fuel and forget motor. Change the Cam Chain, Stator, and Mechanical Seal every 40k-50k miles, that engine will last damned near forever. You can run it lean, you can run it rich, hell you can even run it on one cylinder, or with the high output of the stator fried as long as you don't need to go faster than 50 miles per hour.
CX650- Add Starter Motor and Starter Clutch to the above list. CX650's do not like starters.
I do not have first hand experiences with this, but scuttlebutt is that 650 engines don't like living beyond 80k-100k miles.
Something about the way the engine was designed, the counterbalance is not as synchronized as a CX500 motor. Harder on the piston rings and bottom end shells.
(650T's are exempt from this problem because of heavier duty parts, but they have soft camshaft lobe issues)