Brad Pitt turned down the lead role of Will Freeman on the grounds that it was implausible that someone so attractive would need to pretend to be a single father to meet women. He nevertheless appears in the film (sort of) - he is on the cover of an issue of "Esquire" magazine that Will is reading in his flat.
In the novel, the music that Will introduces Marcus to - and so in turn bonds with Ellie over - is not rap, but the band Nirvana. The book is actually set during the 1993-1994 period, and the story climaxes with the kids learning of and being affected by Nirvana lead singer Kurt Cobain's 4/5/94 suicide (which within the context of the story has additional significance for Marcus). The title of the story is itself a pun on the Nirvana song "About A Girl".
The shot of Will reflected in the mirror when he is depressed was actually taken when Hugh Grant was taking a break. The directors noticed him doing this and from behind he looked depressed, so they shot it without him knowing.
As Will describes web-based research as a "unit of time" in his day, he is seen typing the URL supermodelswithseethroughtops.com. This is actually an active Web site consisting of only a picture of the Pope, Pope John Paul II, in his "Pope-mobile".