I'd say the area between San Francisco and Navarro, I probably died a hundred of times trying to reach the base alone xD Jokes aside, probably San Francisco or Vault 15 + Squat. For Vault 15 maybe was just me, I tried so badly to find agreements with NCR but never managed to. I felt dumb af. And not being able to "save" the doctor after killing all the raiders... :/ Oh, let's not forget about Arroyo. Since it is our village, I think it should have had a bigger impact... I mean, you start there, do the few quests available which grant some easy EXP to begin, and probably never come back for anything (except if you bring the GECK back before going to the oil rig).