I would definitely use an iron-on interfacing. I've used a very lightweight one made by Pellon and it has worked well. The quilt stays nice and flexible, but the t-shirt parts don't stretch and bunch during quilting.
In planning a t-shirt quilt, I like to chart my layout on graph paper. I just make a list of the t-shirt designs and colors, then draw boxes in on the graph paper, writing simple information about each design (subject matter & color) in the boxes, and rearranging them until I'm happy with the layout. I also like to use sashing between the t-shirts, especially if they are varied in color.