Depends on where I'll be reading it and how long the book is. For anything under, say, 300 pages I like a paperback (unless it's mass market, then anything under 250). Shorter books are more comfortable in paperback as they can easily be held with one hand, plus shorter books tend not to stay open as easily in hardback--no weight to keep the spine open. Anything over 450/500 pages I definitely prefer a hardback as they start getting too thick to easily hold in one hand. Between the 250/300 mark and the 450/500 mark my preference goes aesthetic and depends on the book, where it's going to go on my shelf, and whether or not I want it to match other books by the same author.
The one exception is anything that comes from the library or is more than twenty years old. Then it's only hardbacks, because paperbacks just don't have the same old book smell that hardbacks do.