Are there any generic rules-of-thumb for what variable cap (tune and
load) spacing is necessary for RF amps in a certain power class?

For example, "if you're building a 80W amp with a single 6146B the
plate spacing should be x inches".

Wasn't there a table in the ARRL handbook along these lines?

I'm guessing it depends on both the DC plate voltage and the power
level and maybe how mismatched the antenna is.

Of course, I could just buy bigger and bigger spacing surplus variable
caps until they don't arc over when I key up! Sort of how like they
put the weight limit on a bridge by building the bridge, driving bigger
and bigger trucks over it until it collapses, and then rebuild it with
the weight of the last truck that made it over :-).

Tim.