Here are some of the mistakes that make your web page hard to read:

Low Contrast

Grey text on a white background may look cool (I used it once till my readers complained) but your visitors will be squinting by the second paragraph (or worse, leaving your site). Go for high contrast to ensure your text is as readable as possible. Black text on a white background provides best readibility. White text on black is the next best option.

Wide columns

The reader's eye can get lost if it has to follow text all the way across a screen. Avoid having wide text. Dividing your text into multiple columns is one way to solve this but the 'liquid flow' nature of HTML makes this problematic. The more common approach is to use left and right margins. These can be navigation bars, boxes with information, tower ads or simply white space (which doesn't have to necessarily be white - I just mean space with no content). Design wise, I'm a big fan of white space although lately I've been creating sites with so much content, I've had to utilise left & right margins in order to fit everything on the screen.

Long paragraphs

Reading long paragraphs is also tiring for the reader. Break your text up into smaller paragraphs - the reading equivalent of taking a breath. Using subheadings for each section also helps the reader scan the page more easily.
Another way to break up your paragraphs is to highlight key words and phrases. This can be done by bolding, italicising, bullet points or hyperlinks (of course in the case of hyperlinks, you'll need another page to link to - this is a good way to draw readers further into your site).

Long pages

Similarly, web pages that are too long to scroll down are hard to read and difficult to navigate to an exact spot. Instead, break it up into several pages. From a mercenary point of view, this also beefs up your website's page views. :-)

Too many navigation links

When you have too many navigation links (eg - down the left margin), it's too much for the user to take in. The human eye deals best with groups of no more than 6 objects. So either trim down your links, separate them into sections or use my latest flavour of the month - pop-out navigation menus.