I'm gonna go ahead and limit myself to one game per series...otherwise my top five would be nothing but Metroid and Zelda. XD
1) Metroid Prime. It simply took everything great about Super Metroid (which is an amazing game in its own right) and added even more depth to both the gameplay and the plot. Its sequels are also top-notch games, but this is the strongest of the three imo.
2) The Legend of Zelda: Twilight Princess. Yes, I know Ocarina of Time is the most critically acclaimed title in the series history, but I think the characters, atmosphere, and overall plot of TP are just so much better than OoT.
3) Fire Emblem: Radiant Dawn. I just love the way the plot from Path of Radiance was built upon and how the way that the gameplay was vastly improved upon, even if the various factions and armies are vastly unbalanced. Seriously, how many characters in Micaiah's army have a shadow of a chance in endgame compared to those in Ike's army?
4) Oddworld: Abe's Oddysee. Okay, this is a series I regrettably never got into outside the first game, but that first game is a great one. I love the whole idea of playing as a frail and delicate character who's only chance of survival is dodging traps and the use of his ability to possess simple-minded attack drones.
5) Pokémon HeatGold/SoulSilver. I trust no elaboration is really needed considerign the crowd this website caters to. XD
Honorable mentions: Golden Sun series, Megaman series, Kingdom Hearts series, Myst series, Monkey Island series.