This problem has different solutions depending on how you want to play.
If you're just looking for the achievement, one solution to your problem is to do whatever missions you want, choosing the side of good, until you get relatively close to your level point. Then go into a town and steal (for minor karmic reduction) or lay waste to entire towns (for major karmic reduction). You can quickly lower your karma this way. Then, once you're neutral, go kill some random creatures until you level.
(If you're looking to steal, a good place to do it is at Dukov's place… he's got stuff everywhere.)
The "nice" thing about this system is that if you stay on the path of "good" the whole time, you can do this at each achievement point: be bad until you get to the right karmic level, level up, get your achievement, and then restore a save to get back to your good self. You can quickly get "good", "neutral", and "evil" achievements for all levels on one playthrough this way.
(I did this, because I don't really enjoy long-term playing as an evil character… but I do like my achievements!)
You could also do this as an evil or neutral character, but it's much easier to quickly drop from "good" down to your new goal, than to work your way up.
If you find that you're close to leveling, and you're at the right karmic level, and don't want to take a chance on changing your Karma by doing a story-type adventure, you can always go wandering looking for random bad people to take out. Going near the Washington Mall can get you some XP fairly quickly, and you can go inside the capitol building and clear out large areas without picking up any Karma, positive or negative.
Unfortunately, I'm not sure your goal is achievable, as there are generic citizens in some of the major cities -- "Megaton Settlers" and "Rivet City Guards" for instance, that while you may wipe out all of them for once, they will eventually respawn.
The other issue is that you are unable to kill children (with good reason!) so the children within Megaton, Rivet City, Little Lamplight, and assorted other locations will still be around.
As to actual ramifications, the biggest would be repair. Some of the best armor / weapons in the game (or at least, the most unique) are either hard to come by replacement parts, or flat out impossible (in the case of T51-b Power Armor, Chinese Stealth Armor, etc). You'd want to make sure you either only use equipment that you can repair on your own, or face the grim reality of your coolest toys breaking.
Though after you've killed every killable NPC, what exactly do you have left to kill anyway, hm? :P
Best Answer
You don't lose anything when you go to Point Lookout, you continue to use all your gear - it's just another area you can go to. Like the other DLC-only regions, however, your companions will not accompany you to Point Lookout, but you can find them back in their "home area" when you return.
If you don't care about spoilers, here is where you can find the list of possible companions, and you can click one of them to see where they go to when you embark on a DLC area.