Part of me wants to go out on a limb and say Hunter Hunted. Just part.
The rest of me has to go with King's Quest VI. It edges out Space Quest V mainly due to the excellent voice work and the number of options available for solving the puzzles, and Gabriel Knight: Sins of the Fathers because I found the world a bit more interesting than relatively true-to-life New Orleans - and because the transitions felt a bit less arbitrary. I gained a new appreciation for the former two due to the Let's Play process and exploring each one a bit more, but King's Quest VI just amazed me with the amount of extra dialogue and hilarious descriptions for doing things you'd never think of. (Unfortunately, I don't have any of those videos online anymore, but I suppose I could upload them to my Youtube account if there's any interest.) I did almost an entire video of just using every inventory object in the game on the guard dogs and Death because so many of them had unique responses. If any other Sierra game has that much depth, I never found it.
Honorable mention goes to Freddy Pharkas: Frontier Pharmacist just for being awesome in general. I can't give it the victory because the CD version removed the truly excellent responses for using inventory items on each other in unexpected ways. Some of those interactions were even clues to puzzles.