Speakers this way, or that, with cathedral ceiling

Everything else being equal I'd try firing the speakers down the room parallel with the ridge of the ceiling. I've never had success with speakers placed under a sloping ceiling. And, I'd think it would be even better if you were firing down the length of the room with your speakers out several feet from a short wall. But that is just a guess - You really need to do a rough set up in your own room and see for yourself, pick the sound that appeals most to you. The differences should be fairly apparent. Obviously the dimensions of you room are an unknown but important factor.

If the shortest dimension of your room is 16 feet (or more) it's best if you can place your speakers (centered, of course) on the long wall. This allows two things to happen:

1. You can pull the speakers (faces) out 3 feet from the wall behind them (mandatory with planar/bipolar speakers), and you can sit (with your ears) 2 feet from the wall behind you. This allows roughly 11 feet between you (your ears) and the (face of) the speakers -- which is enough distance to put you beyond the "nearfield" listening configuration (AKA, the "speakers-as-headphones" layout ;--)
2. The short (end) walls, now being relatively farther away from you and also farther away from the outside edge(s) of the 2 speakers, than in the "short wall" setup, the path of secondary (sidewall) reflections (speaker-to-sidewall-to-you) becomes so much longer than the path of first arrival sound (speaker-to-you) that even without any sidewall absorption, the soundstage is not compromised, and the volume of the room is fully utilized.

So in a normally furnished room (carpet, maybe drapes, a typical upholstered furniture grouping -- coffee table, end tables, bookshelves (or drapes) behind the listening position if possible, you shouldn't need any "room treatments" except possibly bass traps, if the room develops standing waves -- and with cathedral ceilings, that will be unlikely.

As for those cathedral ceilings, mostly they won't be a problem. Yes, they reflect stuff, but, like with the sidewalls being far away, the secondary reflection path length is too long for your brain to combine it (timewise) TOGETHER with the first arrival sound (which when THAT happens is what screws up the audio hologram ;--) Low flat ceilings are a problem, not high angled ones. And if you are using panel speakers, or line arrays, like Pipedreams, or tall ribbons like Dali's, you won't have problems even in a low ceilinged space because those speaker types have almost no vertical dispersion anyway.

I can vouch for pretty much everything Nsgarch recommended. First, the caveats: we technically do not have a pure cathedral ceiling (it rises up to clerestory windows on a high wall so the room is not symmetrical) and we couldn't sit 2ft from the back wall. Other than that - way back when (pre-kids, etc.) I stumbled onto that type of placement purely by accident. The speakers were centered on the long wall (facing the higher-wall clerestories) and the only real room treatment-like thingies were the drapes over the two sliding patio doors to the outside of either speaker. Lost count of how many friends/visitors commented/marveled over the sound. Same speakers on the end wall were good but never as special. For that & the reasons cited by Nsgarch we recommend you start centered on a long wall and see if you ever move them.

Thanks for your help on this. It will be a whole new world for me, something I've never experienced. Looking forward to it all.

I'm in the same situation as you. If either works, place the speakers along the wall where the ceiling is lowest, pointing toward the wall where the ceiling is highest. Think of an amphitheater -- sound projects out. placing the speakers along the 'high' wall pointed toward the 'low' wall is like listening from the mouth of a funnel. You'll likely experience more ceiling reflection that way.

Unfortunately my speaker position is the undesirable latter situation. More then one acoustic tech has suggested rotating my setup 180˚ for the above reasons. I did try it briefly, unfortunately it didn't work out from a layout standpoint. However, there did seem to be an audible improvement while they were in this position.