I've only read Mason and Dixon once.
I prefer The Crying of Lot 49 because it basically says most everything Pynchon has said that is worth repeating in less than 200 pages. His other books, the tomes, they have their good bits and great bits, but they are endurance tests, and you won't find a person on earth that says the ratio of greatness to meh in Gravity's Rainbow comes close to matching that of Lot 49. The Crying of Lot 49 is his slimmest book, and there's not an ounce of fat on it.
Of his big books, V. is the only one I have read in its entirety, more than once. I bought Gravity's Rainbow last year again, but I have only read bits. I can't do the slog again.