Not as hard as you might think, first 10 stops or so right at the left door(with doc bin snuggled in somewhere), behind(center row) it another row more stops, and the final town of the day is just bulked into the rear, I'll set those back at the left door after I have room. Anything really "large irregular bulk" I'll put on the right door.
I'll also consolidate smaller boxes into doc bins, based on area.
With Multiple doors it's much easier than an econoline.
The wheelwells are also slotted so if you were really ambitious you could put a 2x4(2x6) if you wanted to section the floor. I did that on my econoline/GMC panel van years ago, kept my stuff from sliding around, ended up cutting 2x6's for a few other drivers in the station.