I use the same set of play buttons for my 4-way, my 8-way and my trackball and it feels completely comfortable and natural.
I actually wired my trackball buttons up as the player start buttons and credit button as I found that to be the best solution, as many emu's won't let you map mouse clicks, so putting them as normal buttons was right out, but I didn't need start and credit buttons for other emus, so that is what I did.