Having been a Mac user for slightly more than a year, and working on several different monitors with quite different specs has opened my eyes to the absolute necessity to test your design on a variety of monitors before rolling it out (leaving aside the challenges posed by designing for mobile web devices).
I’ve lost track of the number of times I’ve been on a website that I can tell instantly was not field-tested in this way, a problem that manifests itself most obviously (and annoyingly) in the prevalence of unreadable font/background-color combinations. I may be (barely) able to read that #f7f7f7 font on #ffffff background on my Mac laptop, but there’s no way I’m seeing anything on the 25-inch CRT + Windows XP + non-ideal lighting conditions I’m using at my day job.
Moreover, I find generally that anything that looks like just the right size on the Mac laptop will probably look just a bit too big on most PC monitors. And that light-green background for the sidebar? Chances are that if it’s going to look anything like green on my work monitor, it’s going to more closely resemble a gray-green on my Mac, unless I get the screen at just the right viewing angle
The way I generally try to overcome this is to use a similar approach as I do with web development: develop in the best-possible-world scenario, and test extensively in the real-world-scenario. For my web development, this means developing with Firefox and/or Opera and testing with IE6 and 7 (include Safari somewhere in there).
For design, this means developing with a 19-inch LCD screen intended for PC use plugged into my Mac (with obligatory DVI adapter). You get a rough and ready idea of how your design is going to look on two different and fairly common types of monitors. Then, of course, test again under less-ideal conditions (older CRT monitors with some bad office lighting).
I’m sure there are much more rigorous approaches to this sort of testing, but this is a good baseline that my years of web browsing suggest is not nearly as common as it should be. Strangely, the worst offenders are usually design-oriented websites by people who should know better. I’ve never understood why “looking cool” is more of a design priority than “being usable”.