Fallout 4 is an exception as its also very CPU and RAM dependent. But anyhow, running VR at high resolution and the problems within, has not much to do with in-game settings.
Once u go high resolution at framerates way above 60fps on TWO panels at the same time as we do in VR, then you will no longer benefit much performance by simply disabling some in-game setting or feature. The GPU still needs to render a certain amount of pixels to two panels. That needs high clocks. Thats a challenge, and as long as GPUs doesn't get much higher clocks and more shader cores, nothing will help.
Also you need to remember for VR you are always rendering a much higher resolution than the native screen panels. Just because screens are 2560x1440p doesnt mean you are rendering the same resolution. Its way above that. And remember, we talk about two panels, PLUS a mirror view. In 80-90fps.
As an example, Vive Pro resolution is 1440x1600p per eye. What SteamVR renders to the Vive Pro at SS 1.0 is 2016 x 2240 per eye. Mainly because of the way it projects the distorted image onto the panel and corrects it. So to maintain good sharpness throughout the visible panel area, the total rendered resolution is higher from start. Now think about it. Pimax is 2560x1440p input...