You can never tell just what your users are going to do. Sometimes, their browser settings aren't quite optimal for your site, and you are forced to cater to the lowest common denominator. For instance, if you have a lot of data to display, it would be great to take advantage of the extra screen real estate provided by 1024x768 resolution, but this would alienate your 800x600 users.
You can design for 1024x768 resolution, but make sure to use cascading
stylesheets for just about everything. Then, create a new stylesheet (or set of stylesheets) that will make your pages look OK on an 800x600 screen. Since everything will be bigger, you can shrink the font size and make many other optimizations.
Finally, take out the tags that reference the stylesheets. Add a script to the top of each page, right after the