It's tempting to nominate the DC-3, of course, but it was the Boeing 247 (first flight 8 February 1933) that set the standard for all modern civil airliners to follow. It was the first aircraft to include major design, structural, power plant and instrumentation advances in one package. Consider the list that includes all-metal, semi-monocoque construction, fully cantilevered wing, wing flaps, retractable gear, NACA cowlings, variable pitch props, trim tabs, deicing boots, autopilot and single-engine capability. It's impact was such that it crossed the US from east to west fully 8 hours faster than the Ford Trimotors and Curtis Condors it eclipsed. And it was, unfortunately, also the first airliner proven to be deliberately destroyed by an explosive device. While a victim of its own design limitations, it nevertheless was a game-changer - forebear of those other great Boeing game-changers that would be runners-up in any "greatest civil airplane" competition. Namely the 307, 707, 727, 747, 757/767 and 787. My two-cents worth. Thank you.