I'm now automatically passing over people who start their cover letters with "Dear Sir:". Not all geek wranglers are male.
People who add a salary preference to their cover letter (I think Monster does this automatically) give me critical information. If you're looking for $20/hour, you're definitely not a senior sysadmin.
If I didn't pick out your resume the first time I saw it, I won't pick out the fifth copy either. However, if I did pick it out the first time, it gets un-picked.
Send me a cover letter that's targeted to the job. Catch my interest, and explain exactly why you're a great match. And show some freakin' personality if you can... when you're trying to stand out from 100 other resumes, it will make a big difference.
Spelling. Grammar. 'nuff said.
Make it easy for me. You get five to ten seconds to catch my interest, and may be another minute to convince me you're a good fit. Use that time wisely.