For me I tend to start with rough lines and then fine-tune them at the pixel level.
As I'm not much of a mock-up sort of person I tend to not bother with testing the size, I just start making a tilemap straight away. Having said that, 16x16 is a nice tile size to use for this.
As for 5" phone vs 24" monitor, render your game to a 160x144 canvas/image/FBO/whatever and upscale that.