I agree that it really depends on the setting.
Olympions, Norse, Egyptian, etc. Pantheon type gods are inherently challengable because they are less abstract. They are factious, warring and often petty and cruel. Gods like this can kick off on quite a number of occasions. (Set going to town on Osiris, Loki killing a few minor Godlings, etc.)
I could see the characters challenging a God of this manner, as there are great precident for it. FR is full of histories where advanced civilizations have ruined many a God's day, (I think one group actually emptied a pantheon). Planescape is full of God kicking it Goodness, the Astral being littered with their bodies. There are even a group of Athar dedicated to the destruction of the "False" Dieities. (They haven't done much, but planescape is like that)
The Gods I could see being unchallengable are the ones that are simply manifest ideals or concepts. Water, Fire, Air, and Earth all could be Gods and so long is they didn't manifest into some form of humaniod incarnation, it would be very difficult to destroy them. Ao or other overgods are the unchallengable forces to the extent that they are actually supreme beings in their spheres.
Can God's be slain by PC's? Only if you've gotten some serious firepower (20+ levels of pain, sweat, and tears), especially on the magic front. It would definately being an extreme special cases death as well, based on the manner of God they are.
For your God of Darkness, you would need Weapons of Forged Light to strike at him, and to slay him, his heart would have to be placed in the font of Purest Light. However, his power wouldn't dispear. I would have it pass to the PC's as a collective whole. Suddenly they are tainted by darkness and lords of that God's Dark army. His Duties in the Celestial Spectrum would fall to them, as well as any consiquences for killing the previous God.
It forces the, do we slay our enemy only to become him or do we defeat him, knowing that he will return. Of course if they did it for power, then things get interesting, as they begin to turn on each other or the other Gods. This would get messy. But it would be a fun ride.