Generally speaking one should go as high in volt as warranted by the manufacturer(an know to be reliable) as volts help to make amps go "through" and hence power by the same token circuitry easier.
Keep in mind the ohm law:
i = v/r
i = amps
v = volts
r = resistance in ohm
Meaning for example that if a Tamiya connector is good for 20 amps at 7.4(2s) volt then at 44.4(12s) it should be able to hold at 120 amps!
Now if you keep in mind that watts(power which is a direct measurement of work or for us how fast you can go)= volts X amps...
7.4v X 20 amps = 148 watts. So that connector could let pass 148 watts continuous a 7.4 volts.
Now at 12s, 44.4 * 120 = 5328 watts. So in theory Tamiya is probably okay for HV setup.
Basically it's a square law. If you double the voltage you can pass two time as much current for a total of four times as much power.
Of course a too high voltage will short-circuit your material...
If you aren't bound by rules it's generally better to run as much voltage as possible.
Moral of the story? It's harder on a controller to to run 150 amps at 4s than 100 amps at 6s if it support it. It might even be harder to run 150 amps at 4s than 150 amps at 6s. I say might because controller are complex device that might have more limitation than simple Ohm law and that i want to cover my ass.