I cannot do better than refer you to Bones' combat guide at the link below. There were some flaws in the original v1.0 game which meant that it was more effective to wield a single weapon than dual weapons, but since then there have been two official patches and a number of unofficial ones. I believe that some of them have gone some way towards compensating for this, but I'm afraid I have no idea which patch has done what.The most damaging single weapon in the game is probably the relic sword Hades, provided that the opposition you are attacking is not immune to poison. If it is immune to poison, you do most damage with the relic spear Poseidon, and the best combination of weapons is Poseidon in your right hand and Hades in your left.
You are absolutely right in thinking that the first high-tariff monster that you can usefully multi-loot is the gold dragon in the Temple of the Snake in Blackshire, but with an SSSS party having Fly and Meteor Shower, it is both easy and safe to kill supreme titans, as long as you take a modicum of care to stay far enough back so that you can dodge their ranged attacks.
