When I make boards, I usually set the isolate value to one of two. If it is a densly packed board with limited space I use 12mil, whereas for large boards with lots of space I use 24mil. I have never had a problem with either.
If there is no soldermask, it is best to use a large isolate - say 40mil to reduce the risk of solder bridges.
For high voltage (I did a board with a 240V relay), I used two polygons on the same layer, one around the relay, one for the rest of the board. I set the Isolate next to the relay to 150mil to keep the ground away from the HV for safety reasons. (For even higher voltage - 27kV flyback transformer anyone? I would go even larger, say 500mil, or even remove the ground plane in that area all together to make sure there is no arcing).