I played a lot of 4 on 4 in VA back in the early 00's and what worked best was 2 wings, a defensive minded center and a full time defenseman. It was common in roller hockey to do this back in the 90's as well for 4 on 4. There's a lot of factors to consider, but if you stagger your offense to have to wingers down low and a defensive center roving around the high slot, while your defenseman covers the blue line (if you have a blue line, some 4 on 4 play without a blue line like in roller hockey). The defenseman definitely gets his work out if the center doesn't pull his weight, but when things mesh right, it works great offensively without being too much of a detriment defensively.
If the other team is faster or has a better offense, I'd certainly recommend 2 full time defensemen. The only problem with that is you sort of box yourself in on the breakout and it can be a bit difficult to set up a cycle offensively. The other teams defense just has to rocket the puck to the far boards behind their own net to one of their wingers and they have a solid lead on a break out.
Just things to consider. No matter what you go with, try not to pin yourself too deep offensively, as you don't have the extra player on the ice to help with the back checking/neutral zone duties when the other team is rushing back on your end.