Unfortunately WDC's data sheets have had a lot of problems, and sometimes we're on our own to experiment and find out what the truth is. With a quick look at the
W65C21 data sheet (.pdf), I immediately saw quite a few very questionable things. The good part is that usually the parts are a lot better than the data sheets say.
I do believe you'll find they'll work down to 1.8V or even lower, at reduced speeds of course. I think you'll also find that the pin drivers are
extremely strong compared to what the W65C21 data sheet says, as is the case with the '22 and the '816, per my experiments.
I would still encourage using the '22 rather than the '21 though. I have not used the '20 or '21 in decades; but one thing I remember is that writing to their data-direction registers and then reading or writing to the ports, alternately, is very clumsy and inefficient compared to how the '22 does it. So why is that important? Take for example any case where you want to bit-bang a bidirectional synchronous serial port like I²C, 1-Wire, or PS/2, where essentially you want an open-drain I/O pin. On the '22, you can write a 0 to the output bit, then to pull it down, make that bit an output, or to make it a 1 or to read it, make it an input. Going back and forth between accessing the data direction registers and the accessing actual ports on the '20 or '21 takes a lot of steps. You have to tell it, "Ok, now I want to access the data-direction register," and then do it, and then "Now I want to access the port itself, and then do it. The '22 has separate addresses for those registers, so you don't have to make a separate announcement every time, which could be 16 times for a single byte!