I use a 4x5 and, although I am very comfortable with the size, and it packs easily into my backpack for transfer from office to home, I sometimes think that when using thick (impasto) bristle brushes in Painter, the smaller tablet doesn't allow for proper bristle expression.  The bristles seem clumped and shiny.  Can't be sure because I've never compared to a larger tablet.  May just be a matter of brush adjustment.  But, since I don't use bristley impasto brushes much, doesn't really bother me.  All my gallery work has been done on the 4x5.  -Imager