Research the employer and the job requirements as much as possible before you write each cover letter.
Do a bit more "detective work" about the job than simply reading the job listing. The best way to do this is to talk to someone who works there, or used to work there, but this is not always possible. Employers like people who care about a job opening enough to do some research before applying for it.
Keep the cover letter to less than one page, succinct, precise, eager and light-hearted but not too humorous.
Don't over-sell yourself; be honest. If you're weak in one skill area, that's okay, just phrase it as "wanting to continue to develop my..." or some phrase like that. No lies about skills semi-skills or past experience. If you're weak in more than two skill or experience areas, this job is not for you, don't waste your valuable time writing a cover letter, move on to the next job. You don't have to say in the cover letter that you have skills and experience in each and every area the job requires, but mention your best and what you see is the most crucial skills/experience you have that fit the job. One or two paragraphs to describe those skills is all you need. More than that, you're boasting, or even sounding desperate. If you're reasonably qualified, but your resume is in another area of experience, be clear how you have the critical skills for the job, and where that prior experience is in your resume.
If you're young and/or just out of school or college, you probably don't have ALL the skills the job requires, don't pretend you do. Emphasize ambition, desire, deep interest, motivation; say how this is what you WANT to do, and/or what you want to learn to do more professionally. Some employers like to train "clean slates" in the way they want the job to be done.
Make yourself available, home and cell phone if you have both, precise mailing address as well as email address. If you're not within commuting distance to the job, mention in the cover letter your willingness to relocate, or that you have family in X town, close by; however you're going to be on the job the first day they want you.
Never be the first one to mention dollars to a potential employer, unless they specifically require it to be in the cover letter, in which case, be honest, and humble, accept an entry level wage if it's an entry level job. Most employers only require you mention salary requirements if there is a wide range of salaries for that job skill-set in that profession, and where they are looking for at least 5-10 years of directly-related professional experience.
Be brief, be honest, be direct. You have one or two minutes of a reader's time. Allow them to use it well to screen you into their pool of likely candidates.
Oh, and one more thing: Have someone read over the cover letter and resume and job description before you email it off, whenever possible. Another set of eyes spots spelling errors, grammar errors, and mismatches between what you say and what the job opening announcement says. It might make the process longer, but saves time and gets more results in the end, since your presentation has already made solid sense to someone before it is sent to the employer.
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