Are there big differences between Douglas Commercial 3 and Douglas Commercial 4?
The DC-4 was a totally new design in all respects, as can be seen from the planform diagrams (wiki)



The DC-4 was larger, and structurally totally different:


Straight tapered wing (no sweepback)
Straight tubular fuselage, not the aerodynamic teardrop shape
Round fuselage cross-section. The original DC-4E was going to have a pressurised cabin. The later DC-4A did not implement this but retained the circular cross section necessary for pressurisation.
MTOW = 33,100 kg for the DC-4, 11,430 kg for the DC-3
Four engines of 1,081 kW each, while DC-3 had 2 engines of 890 kW each.
Tricycle landing gear instead of a tail dragger, as @Gerry points out.


All in all a larger aircraft, designed from scratch, implementing more modern features of a later age.