I'd say Fear and Loathing in Las Vegas, which is pretty much quintuple-distilled essence of HST. (Do *not* watch the movie first--in fact, I'd say [unless you are a fanatic Johnny Depp completist] do not watch the movie ever, because it's pretty terrible.) Alternatively, The Great Shark Hunt is a collection of shorter pieces, and while it doesn't have the sustained, cumulative brutal frenzy of F&LinLV, it does have his short piece on the Kentucky Derby, which is a classic.

My favorite work of Thompson's is actually Fear and Loathing on the Campaign Trail, but it's going to be much less accessible for someone who doesn't have a good working knowledge of the American political scene circa 1972. *g*