We're All Someone's Second Choice

I recently read an article about how we're all somebody's second choice when it comes to meeting somebody, and that we really shouldn't take it personally. After all, who wouldn't first attempt to go for somebody who is out of their league or just beyond attainable? It's human nature to always try to marry up or to attract somebody who seems like the best catch.

That said (and fully acknowledging that I often contact people that look like they might be beyond what I can actually handle) I do a fair share of blocking, deleting, and not responding to messages that are sent to me. I do have a conscience about it, but let's be honest… If someone is contacting me and they haven't even taken the time to read my profile to find out what I'm interested in and it turns out they're coming from a vastly different place than I am, why would I even bother wasting my time on them? I'm still trying to figure out what the best method is to let these guys know that I'm not interested. I've tried straight out telling them that I'm not interested, I've tried blocking them, I've tried ignoring them. I don't feel any less guilty about any of those. It sucks to be rejected, and I'm certainly on the receiving end of that.

So what's the best way to do it? Which way does a guy prefer to be told? Is it best to just let the silence speaks for itself?

Update: 4/14/14

The best approach seems to be to tell them "Sorry, I'm not interested. Best of luck to you!"
I've been thanked for my honesty more than I've been tormented for not liking them. Seems straightforward enough. Take note, ladies... just be upfront.