You needn't lose too much work area, but there will always be a certain zone where the cutter cannot reach (unless you make your Y axis rails longer than the bed). This is because you want to have a decent distance between the carriages on your Y axis for stability (I went for 200mm IIRC), hence the machine will be at least this much longer than your cutting area.I arranged things on mine so the cutter reaches to within 30mm of the front of the bed, with the "dead space" behind.Decide on what X, Y and Z capability you want then as Jazz said choose whichever layout fits it most convieniently.