The first couple of LED matrix project I did which used shift registers, I tied the enable pin low thinking it would be one less pin to worry about. I've since had a change of heart about enable pins. They're great for controlling the brightness of a display. I've noticed I'm not the only one who didn't think to keep the enable pin accessible because I've seen other people have similar regrets about their LED matrix designs. Hopefully this warning will give you time to carefully consider if you want to control the enable pins or not.
I just recently posted a video I made over a year ago about one of my LED projects (I hadn't previously uploaded the video because I thought it was painfully boring). While I think you're right to worry about the clock line and using a buffer is a good idea, I thought I'd let you know I didn't have any trouble with a 3.3V clock signal driving 21 TPIC6B595 chips. Of course saying something works isn't the same thing as saying it was correctly designed.
What kind of LEDs are you using? It's of course fun to make your own design but if you're tempted to take the easy way out there are plenty of MAX7219 8x8 arrays which would make your life easier. I haven't tried it myself yet, but I believe there's a very nice library for controlling 8x8 arrays with MAX7219 drivers.
Of course the MAX7219 isn't a good candidate if you want to control the brightness of the individual LEDs (not that it's easy to do this with shift registers).
I hope you let us know how your matrix turns out.