Long ago, I was so enamored with Vecna's presentation in Vecna Lives that I wanted to make a small campaign around getting rid of him once and for all. Still being a lich despite being a demigod, he has a phylactery... somewhere. The PCs would have to find it, take it to the heart of the crystal sphere (SpellJammer) and touch it against the obelisk there that dispels all magic permanently. Finding the phylactery would involve speaking to an arcanaloth and invading a demiplane near Pandemonium with technology based demons (cough Doom, cyberdemon boss).
I figured after that campaign, there really wasn't anything else I could challenge the party with. It never happened, though.