Reading from a computer screen is much more tiring than reading from paper. The properties of computer screens are (still?) such that the eye is more heavily burdened than when reading from paper. There are a few ways in which the author/designer can help the reader.
Keep in mind that reading from a screen is much more tiring than reading from paper. You can help by using a typeface that is especially designed for use on a computer screen. There are not many yet, but their number is growing. They are designed to be readable even on such low resolution devices such as computer screens, while remaining attractive at the same time. Nevertheless, even with such typefaces, reading from a screen still is strenuous. You should, therefore, allow your readers' eyes and mind enough time to rest. Don't use long stretches of text, do use ample of whitespace, and include simple graphics here and there &mdash they are easier and less strenuous to grasp and understand. Don't use complicated graphics, though.
At the same time, try yo keep the screen layout simple and consistent. Remember that the more the reader's attention is spent on the “interface” document, the less attention he'll have for its content. A similar warning can be found in user interface research. It applies even more here, however, since the amount of data offered in a hypertext is generally more plentiful and more complex than in, for example, a word processor or a spreadsheet.