I think you are looking at it the wrong way. Different low voltages on the PCB do not damage MCU and neither do currents, unless you somehow apply wrong voltage to wrong pins or send high current through wrong path. But this is a question of correct schematics and careful board layout.
You can also accidentally shorten something on the PCB. Again, this is true for any electrical device and the danger can be reduced by conformal coating and/or proper enclosure, as well as normal precautions of working with electrical devices.
Whenever there is a motor there is noise, of course. And yes, potential spikes and drops in the power lines. Generally, you do not need isolation within the circuit to deal with these. Add proper decoupling, some filters, beef up your bypassing caps and you are good to go.
What really kills the MCUs easily and often is transients. But these usually come from outside the circuit. It is a good idea to fail-safe all the connections of your board to the outside world, e.g. programming and debug ports, communication lines, buttons etc. However even here isolation is usually reserved for industrial applications. A hobby project can get by with just a few TVS components, current-limiting resistors and reverse polarity protection where necessary.
In combination with good enclosure the above should be sufficient. And since you are dealing with motor drivers a good aluminum enclosure would be the best, doubling as protection and heatsink at the same time.