Not sure what you mean by "actual pixel values". Do you mean pixel sizes? If so then yes, projection matrix does not care about pixel sizes. It does not know anything about pixels.
If your doing orthographic UI and using pixels as the unit, you probably want your matrix to be based off a dummy resolution (say 1920 x 1080) and then adjusted by the aspect ratio of the new resolution.
It depends. Sometimes you want your UI to have more (or less) space when window is resized. To place more (or less) items on screen. Like list view in Explorer window - you don't ant UI stay the same based on resolution. You want to see more files on screen as your resolution increases. Up to some point, of course. After that you want to scale text/icons otherwise it will be to small.
But yeah, in some cases you may want fixed resolution.