When it comes to scaling unevenly, more pixels is always better. With integer scaling, other factors will come into play like the quality of the display itself, how much light it's outputting, if the colours are rich, motion blur, display lag, etc. Those are always relevant, of course.
Some old arcade games are 320x240p. which at 3x is 960x720. Other games, like all CPS1/2 titles, are 384x224. And there's everything in between. Scaling those to fullscreen will give uneven results, and a higher res display to do that with will help smooth things out, i would imagine, even with HLSL effects enabled.