When I played the GC version I was really focused on the offset over the should perspective, the precision aiming and the weapon/inventory/upgrade design as the greatest achievements of the game. These aspects still stand out to me when I replay for the first time on 360, but I have to agree with the poster (who I lazily don't quote) who focused his praise on the enemy encounter design.
There is virtually no grind or filler in the game, which is amazing considering its length. Every "new room" is designed with enemy placements, environmental factors and introduction of the next enemy type to provide something new. While games like Resident Evil 5, Dead Space 1/2, Gears of War 1/2 and Uncharted 1/2 have improved the core systems that Resident Evil 4 introduced, none of them provides uniquely designed gameplay challenges in every new room you enter. The game has something in common with the zelda series and the 3d marios in this sense (rejection of repetition, hate of the grind, introduction of new gameplay concepts as the driving force behind the game).