Due to tying into old floor alignment, room layout (long narrow room) and color differences between pre-finish (new going down) and old sand and stain tunring a room to go WITH the joist would be better aesthetics.
To clarify, existing floor 3/4 is getting a fresh sand and stain and carpet in the other rooms coming out. New flooring will be 3/4 pre-finish micro bevel of Shaw or such. Due to the aesthetics it would look much nicer to turn the room and run the new 3/4 parallel with the joist. Floor in question is over a finished walkout, 2x10's and full 3/4 plywood subfloor. Currently nice and level, tight and screwed glued down.

Can I get away with this or will I have some issues down the road from running with the joist instead of right angle to them?

Whats the space between the floor joists? The tighter the better like 16 inches. If you can get under there and block between the joists with 2 x 10" pieces that would help prevent sagging between joists.

16" OC, drywall ceiling below so no blocking possible.
I might could lay 1/4 ply over the whole floor but adding 1/2 has been ruled out by the MRS. due to floor height changes.

Not sure if gluing down some 1/4 would help or not. Seems if 1/4 is attached nice and tight it would be as strong as 1" if there were such a thing as 1" ply!

If you have solid wood for your sub-floor it will be stiffer than a plywood sub-floor. An extra quarter-inch plywood will not help unless you full trowel glue it.