My worst flats were from a broken wire in the sidewall of a tire that hid back inside the rubber when I was looking for it. I didn't know some tires had wires in the sidewall! Went through all three of my spare tubes that day and had to patch one tube on the side of the road when I finally found that sucker. Luckily I had a spare tire, and somebody had an almost full garbage can within 25 yards to dump the old tire in.
Second worse was a transverse cut in the tire, about 1/4" long. After a couple of flats in the same place (with nothing in the tire like glass shard or wire) I finally figured it out. The tire was flexing enough while rolling that the cut was basically chewing the tube until it chewed a hole in it. IIRC I put one patch on the tube, and another on the inside of the tire, and rode the tire until it was worn out (the rest of the way).