In the early 1980's. a PWA B737 departed Yellowknife NWT (CYZF) to Norman Wells NWT (CYVQ). Unfortunately, Churchill MB (CYYQ) was programmed into the flight director. CYYQ is nearly in the opposite direction to the intended flight. The error went unchecked for quite a while until human intervention prevented a near disaster. Keep in mind that vast area of Canada was not under ATC radar surveillance.
Nevil Shute's novel "Pastoral" contains some drama when a WW.II bomber departs on a heading of 320 instead of 302.