In NYC, Bluestockings is pretty hard to beat (+1 to @warshawshaw’s mention of it above!) Smaller selection, but major “quality not quantity” situation. It’s probably my favorite bookstore. I also think that staff picks at McNally Jackson are really on point; I’ve found a ton of great reads that way (I assume most people already know about that one, though).
In Boston, Harvard Bookstore (no official affiliation with the school, as far as I know) is really good. Lol, in linking to it I noticed they have “Harvard.com” – nice. Porter Square Books is also pretty solid, and has a sweet little cafe. And The Trident, which is a decent bookstore and cozy bar/cafe – have spent many hours drinking a coffee or glass of wine and reading at the bar there.
In Montreal, Drawn and Quarterly is a ton of fun to wander around.
And if anyone ever finds themselves in Boulder, CO (my hometown!), Boulder Bookstore is well-worth a visit. Nothing earth-shattering, but a bunch of cozy nooks to read, friendly and knowledgable staff, and a decent selection of new and used books (they put them together on the shelves, as opposed to a separate “used” section, which I think is pretty nice).