Yes, play it through once without mods. The developers did well, and in essence, because of one of their(I believe)mistakes, the game should be relatively short, as experience is so easy to get and you will probably be level 30 in 12 hours of play.
Once you have finished it once, I recommend Project Nevada, NVInteriors, A World of Pain, MonsterMod, and More Perks, as a good start up.
Totally agree, also if you plan on using power armor, i suggest getting Powered Power Armor, it adds REDICULOUS ammounts of immersion with power armor, different types can have different upgrades, recharging your suites battery lvl and monitoring you suites temperature level, also change from thermal to night vision and other vision modes. It pretty much turns Power Armor from just another armor, to an actual interactive piece of machinery that its supposed to be. Its also compatible with Project Nevada (a must have mod in my opinion) because one of its coolest features in my opinion is that when in 1st person, wearing full helmets, glasses, and other things that cover your eyes actually seems like your wearing them with a border shaped like the eye slots and a layer of "glass" that seems like your wearing it, it also gets cracks in it as your helmet or eyewear gets damaged accordingly.
Type 3 body replacer with the armor and clothes replacer for females is also a good one, for guys breezes males.
and my last recomendation, EVE, it changes alot of the effects and makes them better, some of these include better explosion effects, lazer impact effects, much more realistic blood and gibbing effects among others...
aside from getting FOMM to install and manage you load list, id get FNVEdit, this checks your load order for inconsistency's and also allows you to make a compatibility merged patch witch can help reduce conflicts in mods..
Good luck and have fun!