Please see these image references below for a better understanding, note that this all relative to a metroidvania pixel art game targeting PC and Console, probably that's why options like the letterbox integer scale are not too useful in this case whereas it was designed for mobile. Next I'm using The Mummy Demastered as an example as they also designed their pixel art assets and game in 480x270 as the native resolution.
This image shows the original intended design, with pixel perfect at 1080p, also applicable to 4k.
This is what happens in Letter Box Scale option, it is what I am currently using on my game to fit the whole screen, but it deforms the whole image, you can see how it makes some lines thinner and others thicker, it's specially visible on the ground's tilesets and on the player's character design. This pixel deformation effect is also a lot more noticeable in movement.
This would be a Pixel Perfect image zooming in a little, but it's enough to make dramatic changes in the UI but more importantly, in how the levels are designed.
I'm showing this image with the Letterbox Integer Scale for representation purposes, it shows pixel perfect image but imagine having a finished game on a Monitor or TV, or on the Switch handheld with this thick black frame.
And lastly, the intended effect with Anti-Aliasing, and what Shovel Knight do on their game, this would be the ideal solution for games like mine, where the native designed pixel resolution doesn't fit all resolutions perfectly, but in this way, it still maintains virtually the same pixel proportion throughout the image, if you play on a TV it's not noticeable at all, and on a monitor you have to really get close to see there's some smoothness between the pixels, which doesn't hurt because some users even prefer when the pixels are a little smoothed anyway. (Owlboy does anti-aliasing even though their native resolution is 640x360 which fits perfectly 720p, 1080p and 4k, just to achieve a slightly smoother pixel art look and result)
I'm bringing this topic to the community to see if anyone has a solution or idea to share, a custom screen filter maybe that could help with this, I know Construct has Anti-Aliasing permanently disabled, or maybe touch Scirra's team and have the option to enable it, in hopes to help towards this matter.
Anyway if anyone has an idea I'm all ears :)