May be of some very small advantage without a scope whereas quick operation might be required. It would hinder things with a scope in place.
It depends on the shape of the knob. The proper design is absolutely advantageous even with a scope mounted. A longer knob is more beneficial than a wider knob, IMO, as it increases leverage and gets your hand away from the scope. My preferred design is a somewhat stretched, modest, teardrop shape, similar to the Kampfeld Hunter.
