For my first game, I'm primarily focusing on energy weapons, and was planning to eventually bump up melee skills a bit as well. I've been having second thoughts about that though - repair parts and ammunition haven't been very available, and damage output seems extremely low. I seemed to do similar damage with a Cowboy Repeater and 14 skill, and a Plasma Rifle with 65 skill (similar weapon conditions and basic ammunition in both rifles). It seems a little easier to land hits outside of VATS with the Cowboy Repeater as well, though the plasma projectile speed does seem a bit faster than it was in Fallout 3. Another drawback of the Plasma Rifle is that it eats up 2 units of ammunition every it's fired - ammunition which can be problematic (or expensive) to replace.
It's taking me many shots with laser weapons (and quite a few with plasma for that matter) to kill anything, even if I don't get the damage threshold alert on my target; I burned through ~50 shots with a good condition laser rifle and 65 skill to kill 3 lake lurks - which seems like an awfully steep time/ammunition investment. The only exception to my low damage seems to be when I get critical hits, which do enormous damage. I'm only level 12'ish right now, so I don't know what the late game weapon options are like, but so far it seems as though guns are the better option for ranged combat. Anyone else feel differently?
For getting up close and personal - I really have no idea how unarmed and melee compare to each other, since I've not used either one very much at all. Is fighting with your bare fists ever a viable option? I seem to do almost no damage at all with mine, but my unarmed skill is only like 10 or 15 (I think it was reduced by Good Natured?) What are the advantages of melee over unarmed? Is it only the weapon reach? I seem to remember Power Fists having very high damage output in Fallout 3, but I don't know if unarmed weapons still do much in New Vegas or not.
And lastly - explosives. Any opinions? I rarely used these weapons in Fallout 3, and haven't really been using them too much in New Vegas either. With my very low skills I'm not really doing that much damage, but did seem to cripple limbs fairly easily with the few that I've thrown.