When it comes to run-and-gun shooter games, I'd have to say Gunstar Heroes is my favorite. It doesn't have the sweaty machismo and 80's action movie militarism of Contra, and it allows you to shoot diagonally unlike damn near the entire Metal Slug series.
The plot is exceptionally simple, as it should be for this sort of game, and doesn't take itself seriously at all. The Gunstar Twins Red and Blue set out to defeat the Evil Empire, who have kidnapped their older brother Green and brainwashed him into fighting on their side. You have four levels to fight your way through, each headed up by one of the Empire's generals, and then a massive final conflict separated into three more levels and a lengthy string of boss fights. You can go solo, or two players can cooperate simultaneously.
The game begins by letting you customize your character a bit - you first choose whether you want Free or Fixed Shot, the difference being that Free allows you to shoot while running, whereas Fixed allows you to hold still and fire diagonally (unlike what the poorly translated instructions suggest, you CAN fire diagonally with Free shot, you just have to keep moving in that direction while doing so). Anyway, you pick your mode of preference, then your base weapon - a seeker beam, laser, flamethrower or energy pellet gun. Once out in the levels, you'll find additional weapons here and there - you can carry two at a time, and switch between them, or activate both at once to create a more powerful combo attack (example - chaser and flamethrower creates a stream of flame that you can steer after firing). Exploring the different weapon combos and finding one that suits your gameplay style is part of the fun.
You then select whichever of the four levels that you care to, and you're off. The levels are tremendously varied - you'll find yourself hopping up platforms to catch up with a launching airship, dueling it out on the wings of a helicopter, riding an out-of-control mine cart, even playing a weird dice game among other things. The game moves at a breakneck pace and always has a ton of stuff going on, but never slows down or flickers and always feels rock solid. This is basically the game that Metal Slug cribbed it's whole style from, and while Gunstar obviously can't compete with the visuals of the more powerful Neo Geo games it is faster, more inventive, more humorous and overall more fun. You get some nice visual treats not commonly seen on Genesis games - fairly bright colors and sharp designs, and layers of parallax background scrolling. The music is pumpin' industrial techno/rock that is not something you'll remember later or want to listen to outside of the game, but it uses the limited Genesis sound chip well and works nicely as a background pace setter.
Gunstar is a tough game overall, but it has actual adjustable difficulty. Easy mode is actually a cakewalk, and provides a good opportunity to get adjusted to the game and learn it's mechanics. Normal is a good challenge, Hard and Very Hard are like some kind of punishment. You've got only one life per player and can never get any more, but you have a Vitality meter that allows you to absorb a number of hits (and can be replenished with various pick-ups throughout the levels) before dying. If you kick off, you can usually continue from partway through a level. The game is tough but fair; the only exception being a long string of final boss fights with little to no healing in between that is really rough even on Easy mode (though it's partially saved by being really cute, all the main bad guys are in some control room watching you pound your way towards them on a monitor and crazy leader keeps kicking people out the door to go fight you). There's no continues or passwords, but it's a short enough game that it's reasonable to get through it in one sitting.
The game is frenetic and fun and doesn't need to rely on gore and blood to deliver a good time. This is the epitome of what a run-and-gun game should be, it's just a shame that it's over so fast. One of my favorite Sega Genesis games, and highly recommended for two player action.
* Gameplay Video