The most powerful weapon in the game, period, is the legendary blunderbuss the Enforcer. It does retarded damage. If you want something dead-- shoot it with that.
For regular enemies though, I prefer a pistol. Rifles are too slow and firing distance doesn't really come into play a lot in Fable II. At least not distances which couldn't be covered using a pistol normally (or taking a few steps forward.)
Personally, I use a Master Turret pistol augmented with Devastation and Lucky Charm. This is because it's a good blend of power and number of shots. It drops everything in one headshot except for Spire Soldiers, which take two head shots. Though you can take them out in only one shot if you charge(zoom) it just a little. Plus I think it looks cool. Eldritch(?) Hollow Men also can't be dropped in a single headshot... but that's because they lose their heads and keep functioning. Although without heads, they cannot use their magic, or even fight properly. So it works out. Another exception is the unique "assassin" highwaymen who attack you in groups of three. They are different from normal highwaymen in that they take more damage for some reason. These also require two shots (or one semi-charged.)
The Red Dragon pistol reloads absurdly fast and can be fired pretty much without pause, but the bullets are worth less individually (important for head shots.)
Melee weapons are entirely a toss up. Since a successful reversal can kill any enemy in one hit, you can make any weapon work if you're good with the timing. If you want the "best" melee weapon. It's the Daichi, which is the legendary katana. It swings lightning quick, has way more attack power than a katana has any right to, and it's augments are excellent.
