What I'm wondering is, do you think it would be worth sacrificing unique NPCs for these larger cities? Although I can understand the appeal behind unique NPCs, I don't see it as a vital feature in TES. Walking through a real city, not everybody is going to stop and tell you their life story. You won't somehow know the name of every single person on the streets. Imagine an Elder Scrolls game with cities like http://fc08.deviantart.net/fs70/i/2012/083/e/4/balmora__aerial_view_by_lelek1980-d4to7sw.jpg and this http://suptg.thisisnotatrueending.com/archive/15980491/images/1313685156029.jpg.
I think in order to make cities of this scale work, the actual scale of the game would have to be much smaller. Imagine if TESIV had taken place solely in the Imperial City and the surrounding island. Surely, on a more realistic scale, there would be a multitude of other smaller settlements and farms surrounding the city. Instead of 7 or 8 boring cities, we could have one massive, interesting city to explore, and get lost in. Of course settlements on the scale of previous TES games would exist, but they wouldn't be presented as major cities, and this would be a huge boost to immersion.
Obviously structuring an Elder Scrolls game like this would be a major departure from the norm, but I think it could be worth it if done right.