I think it depends -- when you hang the skein, does it twist back on itself? If it does, and you knit with it as-is, it will likely bias because of the added twist. You may want to try washing it and then thwacking it around for a bit to try to relax the extra twist and balance the yarn.
Another way to remedy this would be to make a cabled yarn -- ply two strands together in one direction, then ply two strands of that yarn together in the other direction, hopefully yielding a balanced 4-ply.
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