Orientation has nothing to do with setting them up as left/right. Which seems like a bald statement :)
When you set them up as left and right, they will be left only on one speaker, and right only on the other one.
There is a slight difference in the way they use the speakers when set up as a mono speaker, but you’re not doing that.
The orientation does slightly change, if memory serves, the way the tweeter is used, but not so much as you’d likely notice. I’ve got a pair of PLAY:5s Gen 2, and I use them in both orientations (not simultaneously, mind you), as left and right speakers. I don’t perceive a significant difference in either orientation, but if you do, you can pick (well, maybe you can’t, since that’s what works in your space) which orientation sounds better to you.
But if you set them up as stereo speakers, then one will be the left only, and the other the right :)