The XB-52 and YB-52 Stratofortress prototypes' primary difference from the production Stratofortress was the tandem seating cockpit for the pilot and co-pilot. The revision came about during SAC commander General Curtis LeMay's review of the B-52 mockup which had a tandem cockpit. Classically for LeMay, he didn't hide his dislike of the cockpit arrangement, with his two primary concerns being that with a narrow cockpit, the instruments and controls would be smaller than idea and the co-pilot would be relegated to the status of a flight engineer with a rudimentary set of flight controls. LeMay's view was that the tandem cockpit sacrificed safety and he argued for side-by-side seating which some in the USAF viewed as more suitable for civilian aircraft than a high performance jet bomber.
Side-by-side seating allowed for larger cockpit instrumentation, some of which could be shared on a common instrument panel and the seating arrangement allowed for close coordination between the two pilots who could share full flying duties on long missions. LeMay's arguments won the day and in 1951 the design revision was accepted.
However, the XB-52 and the YB-52 were too far along in production to incorporate the change but it's not widely known that the change wasn't going to be implemented after the first several production aircraft were built. However, delays in the program allowed Boeing to fortuitously incorporate the side-by-side cockpit arrangement from the first production B-52A.
Source: Boeing's Cold War Warrior: B-52 Stratofortress by Robert F. Dorr and Lindsay Peacock. Osprey Publishing, 2000, p44-45.