Well, for regular non-boss enemies, I'll have to go with the iron-shielded fat moblin because he uses up 5 arrows with the fully-powered bow (10 regular ones) and I don't know how many dozens of sword slashes. He depleted me completely of my arrows when I did a certain escort mission for the first time and that forced me to go back, upgrade my bow, buy another quiver and upgrade that as well.
For combos, I hated that room in the sandship with the 3 beamos statues. Alone, they are one of the easiest enemies ever, but if you have to battle 3 of them simultaneously without a dead spot to hide in, things get very ugly...
Another one that kept annoying me is that 3-eyed sand worm. But once I learned to backflip just in the right time this was a piece of cake.
On a side note, I really can't understand how so many people are having such huge troubles with the sandship mini boss. I mean all it takes to defeat him is stab-stab-stab[...]-occasional shield bash/backflip-stab-stab[...] till he falls of, rinse and repeat. The only difficulty is noticing when exactly to do the backflip/shield bash but if you pay close attention that shouldn't be a problem. I found almost all of the other mini bosses harder (notice that "hard" is relative here), like for example the 4-armed stalfos (because unlike in the pirate battle you have to constantly change the way you swing your sword) or the stalfos/skultulla combo (optional miniboss during second Skyview Temple visit). When I went after the stalfos, the skultulla would catch me in the net, making me vulnerable to the stalfos' attack. When I tried to swoop the skultulla, the stalfos got in my way...