At Ole Miss (D1) in Tark many, many seasons ago, I played a zone defense and ran a four guard lineup with one big man. Actually made a Sweet Sixteen or two using that setup. Would generally get killed on the boards, but my guys were athletic and speedy enough to give the other team's bigs fits. You definitely have to make some concessions here and there, but it's certainly fun to try.
Also at Duke a couple of seasons ago, I had a lineup that usually consisted of a PG, 2 SG's, a SF, and a PF/C. But.......the guards I had were so good that their shortcomings were rarely ever exposed. Lost the NT Championship to UNC with that lineup (probably should have won, but I made a couple of rookie coaching mistakes that cost me big time............dammit).