They actually are different...
For the two UP/DOWN D-pads (i.e Mario Bros.) there are three positions that each of the two onscreen character can be in (bottom, middle, and top), and since you can move the two characters independently, you've got 9 unique positions for the two of them to be in at any given time.
For the 4-POSITION button layout (i.e. Manhole) there are only 4 unique positions for a single character to be in at any given time.
What I found when I designed Area 51 using just the LEFT/RIGHT D-pad was that there was alot of variety that could come from the "hazards" in the environment.
Using the two UP/DOWN D-pads I think offers even more possibilities, and requires some very clear design thinking to make a good game using it... I think it's certainly a worthy challenge!