I do not know exactly how to characterize the class of proofs that interests me, so let me give some examples and say why I would be interested in more. Perhaps what the examples have in common is that a powerful and unexpected technique is introduced that comes to seem very natural once you are used to it.
Example 1. Euler's proof that there are infinitely many primes.
If you haven't seen anything like it before, the idea that you could use analysis to prove that there are infinitely many primes is completely unexpected. Once you've seen how it works, that's a different matter, and you are ready to contemplate trying to do all sorts of other things by developing the method.
Example 2. The use of complex analysis to establish the prime number theorem.
Even when you've seen Euler's argument, it still takes a leap to look at the complex numbers. (I'm not saying it can't be made to seem natural: with the help of Fourier analysis it can. Nevertheless, it is a good example of the introduction of a whole new way of thinking about certain questions.)
Example 3. Variational methods.
You can pick your favourite problem here: one good one is determining the shape of a heavy chain in equilibrium.
Example 4. Erdős's lower bound for Ramsey numbers.
One of the very first results (Shannon's bound for the size of a separated subset of the discrete cube being another very early one) in probabilistic combinatorics.
Example 5. Roth's proof that a dense set of integers contains an arithmetic progression of length 3.
Historically this was by no means the first use of Fourier analysis in number theory. But it was the first application of Fourier analysis to number theory that I personally properly understood, and that completely changed my outlook on mathematics. So I count it as an example (because there exists a plausible fictional history of mathematics where it was the first use of Fourier analysis in number theory).
Example 6. Use of homotopy/homology to prove fixed-point theorems.
Once again, if you mount a direct attack on, say, the Brouwer fixed point theorem, you probably won't invent homology or homotopy (though you might do if you then spent a long time reflecting on your proof).
The reason these proofs interest me is that they are the kinds of arguments where it is tempting to say that human intelligence was necessary for them to have been discovered. It would probably be possible in principle, if technically difficult, to teach a computer how to apply standard techniques, the familiar argument goes, but it takes a human to invent those techniques in the first place.
Now I don't buy that argument. I think that it is possible in principle, though technically difficult, for a computer to come up with radically new techniques. Indeed, I think I can give reasonably good Just So Stories for some of the examples above. So I'm looking for more examples. The best examples would be ones where a technique just seems to spring from nowhere — ones where you're tempted to say, "A computer could never have come up with that."
Edit: I agree with the first two comments below, and was slightly worried about that when I posted the question. Let me have a go at it though. The difficulty with, say, proving Fermat's last theorem was of course partly that a new insight was needed. But that wasn't the only difficulty at all. Indeed, in that case a succession of new insights was needed, and not just that but a knowledge of all the different already existing ingredients that had to be put together. So I suppose what I'm after is problems where essentially the only difficulty is the need for the clever and unexpected idea. I.e., I'm looking for problems that are very good challenge problems for working out how a computer might do mathematics. In particular, I want the main difficulty to be fundamental (coming up with a new idea) and not technical (having to know a lot, having to do difficult but not radically new calculations, etc.). Also, it's not quite fair to say that the solution of an arbitrary hard problem fits the bill. For example, my impression (which could be wrong, but that doesn't affect the general point I'm making) is that the recent breakthrough by Nets Katz and Larry Guth in which they solved the Erdős distinct distances problem was a very clever realization that techniques that were already out there could be combined to solve the problem. One could imagine a computer finding the proof by being patient enough to look at lots of different combinations of techniques until it found one that worked. Now their realization itself was amazing and probably opens up new possibilities, but there is a sense in which their breakthrough was not a good example of what I am asking for.
While I'm at it, here's another attempt to make the question more precise. Many many new proofs are variants of old proofs. These variants are often hard to come by, but at least one starts out with the feeling that there is something out there that's worth searching for. So that doesn't really constitute an entirely new way of thinking. (An example close to my heart: the Polymath proof of the density Hales-Jewett theorem was a bit like that. It was a new and surprising argument, but one could see exactly how it was found since it was modelled on a proof of a related theorem. So that is a counterexample to Kevin's assertion that any solution of a hard problem fits the bill.) I am looking for proofs that seem to come out of nowhere and seem not to be modelled on anything.
Further edit. I'm not so keen on random massive breakthroughs. So perhaps I should narrow it down further — to proofs that are easy to understand and remember once seen, but seemingly hard to come up with in the first place.
Best Answer
Grothendieck's insight how to deal with the problem that whatever topology you define on varieties over finite fields, you never seem to get enough open sets. You simply have to re-define what is meant by a topology, allowing open sets not to be subsets of your space but to be covers.
I think this fits the bill of "seem very natural once you are used to it", but it was an amazing insight, and totally fundamental in the proof of the Weil conjectures.