From an agent:
My main advice for newbies is to do their homework. Make sure they are targeting specific agents who represent the kind of book they've written. I HATE getting submissions for sci-fi, fantasy, screenplays, or other genres I don't represent. There are plenty of resources --guidebooks like the Jeff Herman book, acknowledgments pages, plus online sites--so this information is not terribly difficult to find.
What makes a writer stand out from the pack is if they've taken the time to investigate the types of books I do and write a personalized letter. I automatically delete email queries addressed to "Agent" or "Dear Sir or Madam" or "Yo." I also delete queries without any salutation at all, and believe me, I get plenty of them. (Truth be told I like those because I don't even have to take the time to read them, I just hit the delete button).
Writers should be able to describe their project in one short paragraph. They should not launch into a detailed description of the plot. The cover letter should be no more than one page and should include aforesaid description, plus some pertinent biographical information. Begging, pleading, apologizing, being cute and gimmicky generally does not work. Ass-kissing doesn't work either (well, sometimes it does, but rarely). The main thing for writers to remember is that they should always present themselves in a professional manner.