Modulate Parameters on per Pixel Basis
As is, only very few, specified things work on a per pixel basis. I think being able to modulate any given parameter on a per pixel basis would give a huge amount of freedom, which is needed to create more complex materials.
For instance, the position random in the shape splatter can only be applied uniformly over the whole texture space. But if you want to have a gradient control the amount of position random, you can't do it.
I see substance designer as a texture synthesizer, and as much you need time based modulation in an audio synthsizer, you need pixel based modulation in a visual synthesizer.