Modest Nature 255 Sp Atk, 255 Spd Hold Item: Leftovers/Wide Lens
Shadow Ball/Sludge Bomb Hypnosis Focus Blast/Focus Punch Destiny Bond
Modest Nature (+Sp Atk, -Atk) is best. It raises Gengar's special attack, which is already quite powerful. Max Sp. Atk and max Speed enables almost 400 Sp. Atk, and almost 320 Speed, allowing Gengar to outrun the majority of pokemon, and also allowing him to KO many pokemon. If you want, you can put a little Sp Atk Eps into Def or Sp Def to help Gengar take some hits, but as long as he goes up against slower pokemon he should be fine without the extra defense. For the item, Wide Lens is preferable because it allows Gengar to hit more often with Hypnosis and Focus Blast, both of which are innacurate. Leftovers is useful for healing minor injuries, but on an offensive Gengar it can't help out most of the time.
Hypnosis can be used to put any pokemon to sleep, allowing Gengar to freely switch out to another pokemon or allowing him to get a free hit in. In case you foresee Gengar fainiting, you can try Destiny Bond, useful for taking down very special defensive pokemon. Shadow Ball is best over Sludge bomb. It covers psychic and ghost types, both of which Gengar is weak to. Focus Blast covers normal pokemon, which resist Shadow Ball, most notably Blissey who would otherwise wall Gengar completely. Personally I prefer Focus Blast, but Focus Punch can be used in conjuncture with Hypnosis to score a powerful hit. In this case, you may want to consider putting some Sp Atk Eps into Attack, and switching the Modest nature to either Mild (+Sp Atk, -Def) or Rash (+Sp Atk, -Sp Def).
Bold/Calm Nature 100 Hp, 100-155 Def, 0-55 Sp Def, 255 Spd Hold Item: Leftovers/Wide Lens
Shadow Ball Hypnosis/Will-O-Wisp Focus Blast Destiny Bond
Bold (+Def, -Atk) and Calm (+Sp Def, -Atk) are the only natures that would really support this set. You need all stats but Attack for this set, and Focus Punch is not an option unless you wanted to make this into a physical variant and toss that great Special attack stat. You need an even and good amount of defenses all around. Depending on whether your nature raises Special Defense or not, you may or may not want Special Defense Eps. Leftovers is a great hold item for it's ability to restory Hp, but Wide Lens allows Hypnosis a greater accuracy. If you carry Will-O-Wsp, definitely go with Leftovers.
Shadow Ball provides basic STAB, and teamed with Focus Blast hits a good number of pokemon for powerful damage. Destiny Bond is useful to end on. The only move change is in Will-O-Wisp being an option. It has reliable accuracy, unlike Hypnosis, and carries the ability to half a pokemon's attack stat, stopping most physical sweepers in their tracks. Combined with Gengar's awesome speed stat, Will-O-Wisp can be deadly. However, it suffers from lack of being able to hurt pokemon with Guts Ability.