I have noticed that with project Nevada, and a few other mods, the beginning powder ganger fight can be nightmarish (which is fun). Even with IWS, extra town guards I died a few times. Try beating back raiders with energy weapons (tweaked with eve), incinerators, 50cal sniper rifles.
Anyhow after that, the choice is either go down the golden brick road (The way they want you to go, primm, 188, strip). Or attempt to not drop soap and run north dodging rad-scorpions, deathclaws, gangers, fiends. (In dangerous mixes because of warzones mod.
Now, I am really considering just bypassing all that and going to the strip straight off. Using something like the millennium falcon mod (Summon a virtibird to fast travel). Make my gambling fortune, buy some combat armor and fly back to goodsprings. And butcher my way up the golden brick road.
*Shrugs*
So how about you guys/gals, what things do you do in a new game?