I'm going to assume that when you say "iconic city," you're talking about the Big Worldly City rather than the Pastoral Starting Town. More Minas Tirith, less Hobbiton.
So, here are my picks for the major settings. If I left out your favorite setting, it is a direct personal attack on you and you should take it as such.
Dragonlance: Palanthas. It's where Astinus lives. It's where Raistlin lives. It's the place to be (at least, post-Cataclysm).
Forgotten Realms: Waterdeep. I'm rather surprised there's any debate over this. FR has a ton of cities, but Waterdeep is the city, no question.
Greyhawk: Free City of Greyhawk, natch.
Dark Sun: Tyr. There isn't any obvious hierarchy among the Athasian city-states, so I fall back on "What city serves as the focus of the adventures?" That's Tyr.
Planescape: Sigil, of course.
Mystara: Specularum. Or so I will argue. Mystara doesn't really have an "iconic city," but the Grand Duchy of Karameikos is without a doubt the "iconic kingdom," so Specularum gets the nod by virtue of being Karameikos's capital.
Spelljammer: ...The Spelljammer itself, I guess? It is a city-sized ship after all.
Ravenloft: The Village of Barovia. Normally I'd consider Barovia to be more of a Pastoral Starting Town, but let's be honest, anything outside of Barovia is kind of an afterthought for Ravenloft.
Eberron: A quick Google search suggests the most likely candidate is Sharn, but I'm not going to pretend to know enough about Eberron to say that with confidence.
Birthright: Couldn't even hazard a guess on this one.
Ravenloft is tricky, as the Village of Barovia itself isn't anything to write home about. If you're talking about the wider setting beyond Barovia though, I'd state Il Aluk (pre-Requiem) would have been the biggest and most "Londonesque" setting. Sadly, Ravenloft really lacks an iconic city, which is ironic as there is a whole domain that is nothing but a giant city!
reragonlance, I’d agree with those saying Palanthus. It’s the major port city fought over by powers (Solamnics, Istarians, Drafonarmies, Nerakans, the One God) in the books. It’s the home of the Library of Astinius and the Tower of High Sorcery (with its Shoikan Grove). Its entrance is guarded the High Clerist’s Tower (site of at least three climactic battles). While multiple sites around Ansalon have great importance and Istar might be the city of the most important moment (calling down the Cataclysm), Palanthas is the city that’s stood at the heart of the continent’s affairs from the days of Vinas Solamnas to Jaymes Markham.