I have the same issue on my setup as well.
I should preface this whole discussion by saying that I have very poor eyesight (corrected by glasses), but I am particularly sensitive to these types of things. Back in the day my eyes would quickly fatigue if my CRT monitor's refresh rate was off by a HZ or two. Whenever possible I run with larger fonts and ones that are as easy to read as possible. Things like the ClearType tuner in Windows also help.
I'm running Sins Rebellion @ 1920x1200 - Dell 24" Professional LCD - Radeon 7970 via DVI on my i5 2500k with 16GB of DDR3. I am currently running Windows 8, but had the same issues under Windows 7 when I bought Rebellion this summer.
https://docs.google.com/file/d/0BwgUDd2R4aiQcjlUdlhqZjBHS0U/edit
You can sort of see the issue in the screenshot I have attached, uncompressed PNG file.
If you look at the left edge of the Q in Quit, or O in options etc - there is blurring on the edges.
This is just the most straight forward example I can find - but unfortunately Sins Rebellion causes me almost instantaneous eye fatigue.
I reinstalled it tonight, as there have been recent patches, but it is the same eye fatigue for me now as it was this summer.
I should also say that I have previously tried to replace the in game fonts with other True Type Fonts. This largely addressed the fatigue - as other truetype fonts were sharper - but they weren't sized correctly so text didn't fit in text boxes anymore - which made it difficult to play.
I find this very frustrating, I loved the first Sins game and bought Rebellion as soon as it came out.
Unfortunately, since my purchase this summer (2012) I've only been able to log less than an hour in total play time because of how much discomfort the fonts cause.
It would be nice if this issue could be addressed by the developer, or an alternate font provided that fits within the text / menu boxes that is easier to read could be recommended.
Thanks,
Vay