Hey 40alpha, welcome to the forums!
Sorry for the delay in post approval, we've been swamped! :/
If I were to guess, I'd say that besides the more obvious resolution settings that would cause this, I'd think about double-checking the display driver settings for that display.
If I were a betting man, I'd bet your using an AMD card. For some reason my AMD drivers always do some funky scaling on my larger display whenever I hook it up as a 2nd monitor.
The really odd part when it does this is that the scaling is not shown in the driver settings, the driver configuration shows it to be 100%, IE "normal", or unscaled.
However, as soon as I adjust it by 1%, it "jumps" to 99% scaling, from something much farther away, and then I set it to 100% again, and it's fine.
And yeah, interpolation or scaling usually does have a really adverse impact on quality.