NASA/Boeing have the big delta lifting body/blended wing airliner designs that are actually aerodynamically worthy, scale models have flown. But even then such designs are problematic. The main reason all airliners are tube-n-wings is that maintaining cabin pressure in anything other than shapes as close as possible to tubes or spheres is structurally difficult, and requires lots of extra webs, struts, braces etc. and all sorts of extra stress risers and shear points for cycling fatigue to set in.
Composites might free us from this, but so far only a little. The A380 has a more ovoid cross-section etc.