On a Vedder-type anti-spark switch, Is there any need to electrically isolate the drain of the mosfet(s) from the heat sink since the drain is connected to vesc ground?
No need to isolate as long as it doesn’t touch anywhere else. What was your concern?
You dont necessarily need to isolate it but I highly reccomend you to do so. The best way to achieve this is to buy a piece big enough to cover your direct fets. It conducts heat very well and at the same time does not conduct electricity. The same thing is used in FOCBOXes and other applications. You dont need to do it of course but I would simply for peace of mind and safety. You avoid burning your stuff. It is really cheap, roughly the same price of a thermal paste.
Not sure what dimensions you need but have a look here: http://www.ebay.com/bhp/thermal-conductive-pad You can always order bigger piece and cut it so you should be able to find a piece big enough.
Believe it or not I’m a retired EE with experience in electrical safety but I trust people with hands-on experience more than I trust my own instincts. I want to do things right the first time.