One thing that fascinates me most about Planescape is the bittersweet tragedy that can be found in many PS-related storylines (e.g. Planescape Torment, Pages of Pain, Faction War, background stories of several NPCs etc.).
However, I think it's quite hard to create that kind of mood as an overall 'campaign theme', especially if you have to focus on a whole party instead of one 'main character / protagonist'.
Do you include tragedy as campaign theme? And if you do, how?
One main NPC & character contact in my PS game was a Bleaker who had, apparently, purposefully drank Styx water to wipe her memory multiple times in the past. She was the librarian for the Cabal's collection of ancient and disturbing texts, and apparently had discovered secrets she wished to forget entirely, which was disturbing considering the many horrible things she had re-learned and was pretty much fine with.
During another adventure, the PCs destroyed an evil priest's power source: an orb used to collect the souls of sacrificial victims. The PCs were unaware that destroying the orb outright would funnel the innocent souls directly into the Abyss. They did manage to save two of these innocents in a subsequent adventure to the Abyss, but the other hundred or so were irrevocably doomed.