Do we have to pick just one? Because all of these (and more!) are worth playing:
OutRun - Time trial driving game
Space Harrier - 3D shmup where you play as a dude with a sweet jetpack
After Burner - 3D shmup where you play as a sweet jet
Power Drift - racing game
Virtua Cop - Arcade shooter
Virtua Fighter - Fighting game
Super Hang-On - Motorcycle racing game
Virtua Racing - One of the first 3D polygonal racing games, somehow managed to get a very impressive Genesis port
Golden Axe - beat-'em-up
Super Monaco GP - top-down Formula 1 racing game
Daytona USA - Stock car racing game, taking the formula set by VR and perfecting it
Alien Syndrome - top-down multi-directional run and gun
Alex Kidd - classic platforming series predating Sonic
Phantasy Star - SEGA's first RPG series
Shinobi - classic ninja sidescroller
Streets of Rage - excellent beat-'em-up series
SEGA Rally, Indy 500, Manx TT Superbike - More SEGA racing goodness
House of the Dead - Cheesy horror arcade shooter, super fun
Typing of the Dead - Same as above except instead of a gun you use a keyboard
Skies of Arcadia - Gorgeous Dreamcast-era RPG