Sonic the Hedgehog
The classic platformer that sold the Mega Drive and made Sega a star overnight. Sonic 2 and Sonic 3 are superior games in some respects, but it's the original that boasts the iconic levels and hits all the right nostalgia buttons when played today. As a bonus, Sonic the Hedgehog doesn't feature the annoying sidekick characters that would come to dominate the Sonic series in later years. Still thoroughly enjoyable, it's available on Xbox Live Arcade, Wii Virtual Console and the Sega Mega Drive Collection on PSP and PS2.
Streets of Rage 2
If Sonic was the first game that every Mega Drive owner owned, Streets of Rage was usually the second. A side-scrolling brawler in the Final Fight/Double Dragon mould, Streets of Rage had one or two players battling through a gang-infested city, battling thugs and bosses with fists and any pipe, baseball bat or bottle they can grab. The sequel improved on the original with longer levels, branching endings and more extravagant bosses the before, and was one of the finest two-player games to ship on the system. At the time, the graphics and the music were felt to be cutting edge. Available on Xbox Live Arcade and Wii Virtual Console.
Another seminal Mega Drive favourite. EA's motorcycle-racing game postulated that if merely racing high-powered bikes across American was fun, then racing high-powered bikes across America while punching rival racers from the saddle would be even more entertaining. They were right, and while Road Rash wasn't the most technically impressive racer on the system it was among the most compelling. Available on the EA Replay compilation on the PSP (along with other EA Mega Drive hits like Desert Strike and B.O.B.)