In the actual episodes, the issue only appears to arise twice: in whether or not to interfere with the pseudo-Romans in "Bread and Circuses", and in whether or not to meddle with Vaal's disciples in "The Apple". Elsewhere, the Prime Directive or the General Order 1 either is not quoted as part of the ponderings, or has a slightly different impact on the story.
It is perhaps unfortunate that the pseudo-Romans were so explicitly a "primitive society", suggesting the PD applies to those only. The Gamma Trianguli humanoids were not explicitly primitive or advanced as such, but they certainly weren't technologically on the same lines as the Federation, so the impression again was of the PD regulating how our heroes look down on cavemen.
It really looks as if this "PD stops at warp drive" thing was purely a fan invention from the very get-go...