First off, I think the Stack Overflow family of sites is great. I use these sites a lot to find answers. Most of the time I find good content and fairly descent background information.
One thing that consistently frustrates me with the site though is the lack of width of content on the page. I run at 1920 x 1200, and the content of the page takes up only around 40% of the usable area, while 10% is taken up by 'similar questions', and 50% of it is blank whitespace on either side. This might sound minor, but when I'm trying to read someone's answer (specifically code blocks that don't auto-wrap), I get stuck with horizontal scrollbars. It is frustrating to know that the content could probably fit on the monitor, but it's been restricted down and now I need to scroll to see it all.
Also, I could see a lot of users that don't have their resolution set that high, but for programmers (one of the core target audiences), I think high resolutions are fairly common.