The GUMSHOE investigative roleplaying system was designed by Robin Laws over 10 years ago, and in that time, it's been refined and expanded in a number of different rulebooks. One of the guiding principles of GUMSHOE is the idea that the core system should be customized to better reflect the genre of each game that uses it. So each GUMSHOE rulebook is unique and presents a different take on the core system ideas.
With that in mind, here are my top three GUMSHOE system rulebooks. Each one looks at the system from a different angle and that makes for a different game even though each uses the same core engine.
Based on the science-fiction novels of Jack Vance, Gaean Reach is a space opera game of hard luck heroes seeking interstellar vengeance. Unlike the more expansive Ashen Stars, Gaean Reach is fine-tuned to a very particular story: the investigators are out to get revenge on galactic criminal mastermind Quandos Vorn. Character creation is randomized to get everyone into the action as quickly as possible. The rules are streamlined and present a very clear snapshot of the GUMSHOE rules. I often describe Gaean Reach as the ultimate quick-start guide to the system.
On the other end of the spectrum, you have the massive full-color TimeWatch core rulebook. TimeWatch is a history-spanning game of time travel in which you play the officers in charge of protecting history from all who would threaten it. In addition to that main campaign, there are a number of other frames from parallel worlds to the excellent Time-Crime frame (though I may be a little biased there). TimeWatch opens up the throttle on GUMSHOE to probably its most gonzo, and it's always ended up being a riot at my tables.
Finally, we have Bubblegumshoe, from Evil Hat Productions. The elevator pitch is essentially "Veronica Mars, the game," though it can handle everything from that teen-noir end of the spectrum to classic stories like Nancy Drew and the Hardy Boys. Bubblegumshoe does the teen detective genre properly, digging down into the relationships and "feels" of the "teen" part while letting the GUMSHOE system handle the "detective" bits. And the rules for creating your town and all the connections between its important characters is a wonderful bit of tech for any GUMSHOE game that's going to stay in one place for a while. Check it out.