This thread is the perfect excuse for me to paste an old post I wrote for the 25th anniversary of the Sega Genesis.
Starting off, let's begin with this nicely written and extremely informative article
http://www.racketboy.com/retro/sega/genesis/sega-genesis-megadrive-101-a-beginners-guide
I highly recommend people trying the games on this list. Not every one of these games stand the test of time, but a significant majority do and still hold up very well to this day.
Games are listed in not order of favorites, but just selected from memory at the time of writing.
01) Beyond Oasis
Developed by Yuzo Koshiro's studio Ancient. Beyond Oasis is one of two games that is direct answer to Nintendo's Legend of Zelda series.
02) Castlevania : Bloodlines
The only Castlevania game to ever been released on a Sega platform, except being the Saturn port of Symphony of the Night (which didn't get a English localized release)
03) Rocket Knight Adventures
An awesome and colorful action platformer by Konami developed by Contra staff.
04) Steel Empire
Solid Horizontal STG / Shmup with steampunk setting. It's definitely no Gradius or R-Type but again neither one of those are on the system. You have two ships a small and quick but fragile Biplane, and a slower but large and more durable Zeppelin.
05) Crusader of Centy / Soleil
Another great action adventure game that parallels the Zelda formula on the Genesis / Megadrive.
06) Alien Soldier
Very nice run'n'gun action game in the same style of Contra, developed by Treasure.
07) Dynamite Headdy
Highly detailed and colorful 2D platformer, developed by Treasure.
08) Landstalker
An awesome isometric pseudo-3D dungeon crawler by Climax, with solid dungeon design.
09) Streets of Rage 2
One of Sega's best side scrolling Beat Em Series. This is one is my favorite entry in the entire series.
10) Ristar
Awesome 2D platformer by the creator of Sonic the Hedgehog.
11) Shining Force 2
This is the game that got my interested in the SRPG genre, long before Disgaea and Final Tactics, was Shining Force, the 2nd game is the highlight of the series on this list.
http://www.shiningforcecentral.com/?p=games&id=sf2
12) Phantasy Star IV: End of the Millenium
Arguably the best turn based RPG on the system, with a story and characters I had emotional attachment too. With a spell combination system that predates Chrono Trigger and a Tragic Heroine that predates Aerith
14) Gunstar Heroes
Another Treasure developed gem for the Mega Drive. Run'N'Gun gameplay with selectable levels, fantastic music, and large boss fights!
15) Shinobi III: Return of the Ninja Master
In regards to the many Ninja games released during that era, such as Ninja Gaiden, Ninja Warriors, Hagane, and Ninja Spirit. Shinobi III ranks amongst the best of the platforming action titles in this category.
16) Pulseman
Before Gamefreak was known for Pokemon. They made this nice 2D platforming gem on the Mega Drive.
17) QuackShot: Starring Donald Duck and World of Illusion: Starring Mickey Mouse
In a time period when Disney games weren't criticized for being "kiddy" and were respected as a form of video game art, These games stand as an example of this.
18) Contra : Hard Corps
Hard Corps combined all of the great, non-stop shooting gameplay that is expected of this great run'n'gun action series.
19) Ranger-X
A highly unappreciated, mostly ignored action title on the Genesis known for having some of the best visuals to push out its hardware.
20) Sub-Terrania
A very original and unique take on the gravity style of shmups (you know, like asteroids). One of the more obscure games to be had on the Mega Drive / Genesis.
21) Golden Axe II
Much like Streets of Rage 2 improving over it's predecessor, Golden Axe II is also equally superior over the original in terms of enemy designs, boss fights, gameplay and animations.
22) Mercs
Run'n'Gun by Capcom, the second installment of the notable Commando series. However it has an overhead perspective and gameplay similar to the Ikari Warriors but with the inclusion of drivable vehicles (think Konami's Jackal)
23) Sonic the Hedgehog 3 + Knuckles
A technical marvel (at the time). Being able to join two cartridge games and merge them into a single massive game (Dubbed Lock-On Technology). This is arguably the best Sonic platformer of all time.
http://info.sonicretro.org/Sonic_3_&_Knuckles
24) El Viento
Created by Wolf Team and published in the US by Renovation. With haphazard action and iffy level design, but the fast pace and overall craziness make this one of Wolf Team's better titles. It was also one of the earliest games containing a soundtrack from Motoi Sakuraba, in fact Wolfteam itself became the foundations that birthed tri-Ace once after they disbanded from Namco / Telenet Japan.
25) Alisia Dragoon
A an overlooked platforming action title that was developed by Game Arts and had animation designs from Gainax.
I should probably add another 5 games to coincide with the 30th anniversary, As I made a list 10 years ago for the 20th, and this list was used for the 25th. Eventually I'm going to start running out of quality recommendations if I keep adding 5 games for every 5th anniversary. Gonna be pretty hard once the Genesis / Mega Drive reaches 50
but anyways, My 5 additional recommendations to check out
26) Lightening Force / Thunder Force IV
Awesome STG / Shmup by Technosoft and arguably the best showcase of paralax scrolling / layers on the Genesis outside of Ranger-X
27) Road Rash 2
One of EA's forgotten franchises. The 2nd game is notable for me, but the first and third games are no slouch either.
28) Earthworm Jim
An obscure action platformer with some Run'n'Gun elements originally developed on the Genesis and ported to other platforms.
29) Herzog Zwei
An interesting concept by TechnoSoft the mixture of a STG / Shmup with RTS mechanics in needing to control various infantry units and destroy enemy bases.
30) Comix Zone
A side scroller beat'em up with a comic book style aesthetic. Instead of going from level to level. Each area in the game instead is presented as if panels from a comic book and the next level is flip of a page. Also a showcase of some of the best sprite work and background design on the Genesis / Mega Drive.