Speaking of book town, Kanda Jimbocho is famous. If you go there from Tokyo, Akihabara or Shinjuku, you had better walk from Ochanomizu Station of the JR Chuo and Sobu lines. From Shibuya or Nihonbashi, Jimbocho Station of the Eidan subway Hanzomon line is in the town. It is world-famous book town. It is grand sight that many secondhand bookseller are on the north side of the street because of preventing from damges by exposing to the sun. It is inconvenient that many stores have been close on Sunday, but more of them is open.
If I choose one in Jimbocho, it is the Kanda main store of Sanseido, though it is a bookseller of new publication. It is a representative bookseller in Tokyo. It is also famous as the publisher of "Shin Meikai Kokugo Jiten" ---or "New Lucid Japanese Dictionary"---, you know. It makes us feel the pride as an old established and a large scale bookseller. It seems to be good at the books on the humanities, but it keeps a good selection on science. It has the corner for foreign books, foreign maps, reviewed books, SFs and so on.
If I choose one more bookseller of new publication, it is Shosen Grande. Shosen Grande keeps a lot on computers, trains and other scientific books and magazines, and the sister store Shosen Bookmart stocks a lot on lighter ones such as on animation or literary coterie magazines. Shosen Grande has a good selection on computers, though, Shosen Booktower in Akihabara may have more now. It is told that Shosen is the best as buying paperbacks, because they give us lovely book jackets and markers. Thus they motivate me to buy fantasy papaerbacks at Shosen.
About secondhand booksellers, I must say that go around painstakingly anyway. However, if I dare to choose a bookseller, it is Meirinkan Shoten. It stocks science and technological books widely and cheaper than other stores.
You should not miss the Kanda Book Festival that is held from October to November around Culture Day every year. Various publishers sell bargain books on their booths out of warehouses, and there are interesting secondhand books sometimes.