Classics out of printHilzoy makes the first nomination for a book (1) in English (2) more famous than Raleigh's History of the World and (3) not currently in print: Hakluyt's Voyages. The Folio Society published a version, but seems to have let it go out of print, though it's available second-hand at reasonable prices. It's also available on-line, which isn't exactly "in print" but is a close substitute for some purposes.
Hilzoy also points to an important related category: classic texts in other languages not available in print in English translation. Apparently that applies to all the works of Condorcet, for example.