I am recruiting again (a two year bioinformatics postdoc in motif detection) and so my mind has once again turned to the stormy seas of job applications.
Happily, I have already had a few interested parties. (The ad only went live a couple of days ago.) Among them, however, I already have a couple of the "generic" applications that make my heart sink. "Dear Sir/Professor..." (you're emailing me, you should know my name) "...I would like to apply for a position in [insert unrelated research area or, at best, a list of broad research areas that by chance overlap the project area..." (you are applying for a specific project, you should be interested - or, at least, feign interest - in the specific area) "...please see my attached CV/resume and unrelated publication" (presumably in the hope that I will spot the relevant connections that they have failed to).
Getting a job is hard because you never know who you are up against. Writing a decent job application is not so hard, though. At least, not if you are actually suitable for the job. There is a wishlist of criteria, so point out how you meet them and how you are really willing/interested/able to learn the skills that you don't yet have. (Like most wishlists, desired criteria are often up for negotiation in reality.) Mention a keyword or two from the project - the name of the project, at least! - to show that you know what job you are applying for. And, if contacting a specific person, show that you know who you are contacting and what they do.
In an ideal world, you will not have to customise your CV much, if at all, because you are genuinely a good fit for the post. If you are not, though, you will have to do some work. If, for example, your background is in a different field, highlight your relevant experience and compress the pages of irrelevant stuff. If the job really interests you, it is worth the effort. If not, don't bother to waste your time and the poor soul short-listing - you won't get short-listed anyway.
Even if your CV doesn't need customising - and ideally it won't because you will be applying to a job that suits your experience - you still need to put a little effort into your covering letter/email. At the very least, I feel that I am worth the time to look up my name, research interests and the think of a sentence or two about what interests you about my work. If you don't feel that I am worth the time, am I really going to want to hire you? If there isn't enough information, then ask. Show you care. It's not hard. If you don't give me the impression that you care about my work/project/job, I am not going to care about your application. It really is as simple as that.
On the other hand, if you show that you (a) know what you are applying for, (b) really want to do it and (c) have the experience to hit some of my wishlist and track record to learn the rest, I will really want to short-list you, even if someone else looks more experienced/qualified on paper. So, if motifs are (or might be) your thing, you know how to program and you're interested in molecular evolution... drop me a line!