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Depends on the mood.
Fat Mines work wonders.
Ballistic fists and power armor +psycho +slasher + medx makes you feel like iron man trolling the fuck out of the hulk in a hulkbuster.
Graham's .45, the official wasteland gun on utah. God tier reload, crit is crazy high.
man opener from fallout 3. Or gauss cannon. Tesla cannon. Or lure in an albino rad scorpion and let them duke it out.
Am i forgetting something K?
IRL, well i got .308 and 12 gauge slug out the ass so... I guess I have what I have. I also have a bulldozer and backhoe, so killdozering my way to victory could be viable.