Surprising that the Midland route took so much longer. I always thought it was slightly quicker.
I was looking at 1950s GC journey times earlier and it seems Manchester trains stopped at High Wycombe, Woodford, Brackley - quite a few towns you'd think an "express" wouldn't stop at. I wonder how long a Marylebone, Sheffield, Manchester would take.
It would be unlikely that there would be enough passengers to do London-Sheffield non stop, and, when the GC was open, would be quite a job non-stop for a steam loco (although quite possible!)
In 1956 the best train of the day was the 'Master Cutler' which did 6.18pm Marylebone to Sheffield in 3h40 stopping only at Rugby, Leicester [engine change] and Nottingham. The fastest Sheffield-Manchester timing was 55 min, stopping at Penistone, Dinting and Guide Bridge. In those days through trains were booked 5 min for an engine change at Sheffield V. So an overall time of 4h 40min.
The best train on the LNWR route was the 6pm 'Mancunian' stopping only at Stockport, in 3h35min. Even if your GC trains had made only the Sheffield stop, I don't expect the overall time would have been less than 4h10m
The 6.40pm from St Pancras arrived Manchester at 11.8pm (4h28m) stopping at Kettering, Leicester, Loughborough, Derby Matlock, Miller's Dale, Chinley and Didsbury.
In 1965, the Midland Pullman from St Pancras did it in 3h10, and the best schedule by a Pendolino is about 2hr.