To capture what's been discussed above, the differences between a 250/2500 and 350/3500 depend on the manufacturer and specific year model. With the current Ford's, the main practical difference I see is the overload springs on the F350, which helps to keep you off the bump stops with heavy loads. I suppose the higher weight ratings on the F350 sticker is another practical difference, although I view that as somewhat artificial.
At least with Ford, I recommend buying an F350 because the price increase over an F250 is negligible. The problem is there are a lot more F250's out there, so it's easier to find one that meets your criteria.
