It depends on the internals of the muffler. If they are just straight through one side to the other, with perforated tube it wont matter. Some have built in X pipes and depending on the X pipe design, might not flow the best if you don't run them dual in on one side and dual out the other side.
This Jegs muffler wouldn't flow the best if you ran it 1 in and 1 out on each side of the muffler.
Pypes has a straight through design, common on the 70-81 Camaros. Where you can run 1 in and 1 out per side.
So, it's really muffler dependent if you can or shouldn't