Well, in smplayer (also X11 video output) I was having 4k playback without framedrops on not so new hardware (note: direct rendering does not affect anything on Qubes OS to my opinion). But in my case the display resolution was smaller, it can matter.
But we a talking about avoiding only frame drops, not flawless playing. Because Qubes OS is not able to play flawlessly even 1080p video in any player or browser. Everyone can check the panning video on youtube and understand this statement.
This problem happens due to X11/Qubes OS limitations, so nothing can be done at the moment, as I understand.