I like to have my line work on top set to multiply (I change the color of the line work so it's more of a dark red or orange rather than black I'll also make the pixels a bit transparent by adjusting the opacity of the layer if my line work is too dark). I work below on regular layers as much as possible. Then when all my color choices are made and worked out I'll have layers above the line art to polish. The line on top seems to work better for me especially if I have shaded or hatched with the line work. Having changed the line work to a dark red or orange helps those shadow areas blend in with the color below.