I run a few small businesses and quite regularly get unsolicited emails/calls.

There's absolutely a real, qualitative difference between contact from a real human being who respects everyone's time and has done actual research, and someone who is just playing the numbers game and blasting as many people as they can (regardless of how "warm" the leads are).

It's a bit of a spectrum, but if someone has taken the time to handwrite and research an email or call, I'll at least try to give them the courtesy of a response.