I personally respond to every donation that has a note in it, even if its a simple thank you. (I may occassionally miss one or two during periods when I am very busy). For donations without a note, I don't acknowledge them, as kiwidude points out, doing so will suck up a significant fraction of my time. I don't like the idea of an automated response, as it doesn't really have any meaning, and simply creates email noise.
I am, of course, very grateful for every donation I receive, the evidence of my gratitude is the continued development of calibre, see:
http://calibre-ebook.com/whats-new or
https://www.ohloh.net/p/calibre/analyses/latest (which shows development activity in calibre).
Indeed, I currently work full time on calibre and that is made possible only by the number of donations I receive.