Most 2D/2.5D drawing packages use the normal mathematical convention that the X axis is L -> R as you look at the paper, the Y axis is at right angles to it. How you orient your paper or machine is irrelevant. My machine is in portrait mode and it just makes it easier to visualise if it is the same as the drawing. My Z zero is at the top of the workpiece, but my Z homes to the top of travel. X and Y homes to Left and Nearest me respectively. I just find it less confusing this way and therefore mistakes are less easily made.