The Needler in Halo games may kick ass but ultimatley if applied to the real world I can't help but imagine things could go seriously wrong. I mean it may lock onto an ally by mistake or the explosion radius would be more extreme, all I'm saying is a ridiculously fancy pink needle shooter is ultimatley a lot less reliable then just a good ol' fashion energy sword.
Also as much as I love the Longshot sniper rifle from Gears of War (I've already propsed to it) I have to admit that for a game set in the distant future where people have advanced satelite technology that can level entire buildings.... it didn't occur to us that a single shot rifle is a little inefficiant? I mean all the other guns had clips or rolls or whatever, there was no reason why the longshot couldn't as well.
Next up, the Line gun in Dead Space. I mean sure it is powerful and very useful but I have to be left wondering what possible purpose it would fill in a mining operation that can't be filled by one of the many other tools. Although I'm ready to admit it could be used for clearing out vertical sections of cave wall.
Finally Bioshock's grenade launcher. It's improvised of course and randomly put together but there is no question that despite being powerful and even quite charming, an improvised launcher that shoots grenades made up of tin cans.... is pretty impractical.