And as a matter of fact, I'm not entirely disposed to designers futzing with the user's fonts. Don't leave out these people. Not only are they an important audience, but serving their needs serves everyone's needs by making pages accessible in alternative platforms, such as handheld devices. Test all the browsers your audience will use You can decide not to support a certain browser or platform. But do so consciously, not by omission.
Colors look different on different systems.
Macintoshes and typical Windows displays, for example, differ in average brightness. What looks crisp on one is like mud on the other. Be clear on your pages about what browsers you don't support, as well. If you know some functionality won't work for visitors using Netscape 3.0 on a Macintosh, for example, say so. Better yet, learn to write JavaScript code to detect the user's browser and simply omit elements that aren't likely to work well.