Yes there is a difference. The 350 will tow more weight than the 250. And the longer truck, of the Crew Cab, will make towing easier and smoother, except when maneuvering in a tight spot. It tracks better.
In the 1994-1997 trucks other than springs and front axle they are the same. The front axle in the F250 4x4 is a dana 50 ttb and in the F350 it is a straight dana 60. Both have the 10.25 rear axle. Like Dave said the longer the better for towing.