Match the background to the tone of any background image to aid anti-aliasing. Check in all available colour depths, greyscale, monochrome and a cheap LCD screen. Check usability with your grandparents. I find the best use of colour is to look at complimentary colours, they can provide a very useful tool to producing colours that can blend with each other and be able to work together to produce a harmonious site. I have carried out a research study into this area for my degree and have put together a section on my site that shows the colours available, both in tone and tint combinations.
Emphasis is on using safe colours.
There is also a section on the site which allows the visitor to interact with the different screen colours and see how they affect each other. The site is still under construction, but should be completed by the end of April. Familiarize yourself with subjects like color wheels and the emotional responses evoked by different color combinations and you'll have some powerful tools at your disposal. Transparency is another big helper too. For example, at one pizza store site, I used a tomato color for the main page's left navigation bar.