I think the problem with Planescape is that while it's cool flavor and I love the setting, it's not the easiest setting to run. It's got three problems.
First, the factions don't work that well. They're basically defined by alignment, philosophy, and (often) an associated plane. There's tons of room for political intrigue, but since it's basically all based on alignment and philosophy it's like the most stock and uninteresting political intrigue ever. These factions don't appear to have goals. They just have beliefs and philosophies. Worse, they often feel like they just overlap. Xaositects, Anarchists, and the Cabal are like three different brands of the same flavor ice cream. There's like four factions that are just variations on nihilism. It's cool from 10,000 feet, but on the ground it just paints everyone with a fixed set of predefined stock beliefs that don't really lead to interesting characters. Yes, there's the faction war, but since factions are what people know about the setting it's really bizarre to suggest moving forward with a totally different set. It'd be a totally unrecognizable setting to the majority of players familiar with the original setting or the video game.
Second, the mode of travel to more interesting places than Sigil, or even more interesting places within Sigil, is portals. Sigil is like the World Serpent Inn expanded to the scope of a city. The World Serpent Inn was a fun contrivance for a few campaigns when you didn't want to bother with a narrative to connect the adventures, but it's difficult to construct a consistent feeling world when the world itself isn't consistent. The problem with portals is that you often end up just being pushed around by the plot from place to place. You lose your sense of location in the world and easily feel railroaded.
Third, the Lady of Pain is... not a good character for a campaign setting. Like she's the absolute authority that you can't do anything about. What am I supposed to do with this character as a DM? She's a combination deus ex machina and tarrasque rolled into one. Again, it's cool idea from a lore or narrative perspective, but I don't see how it serves the playability of the campaign setting to have the place run by Judge Dredd or Ultraman. Yeah, she's supposed to stay out of the way, but if that's the case why is she there? To explain why nobody has taken over Sigil? And if she's supposed to stay out of the way, why's she always getting involved with the PCs? It's just weird.