It's honestly a bit ridiculous. Especially when you consider that if you talk to House about it in New Vegas he claims that city was targeted by some absurd number of nukes (77!) that he mostly dealt with. Makes me think nukes in the Fallout universe are all suitcase-sized equivalents.
War isn't simply about killing a bigger number of the enemy's population; it's destroying the things that support them so their infrastructure collapses. Take Rome for instance. Once one of the single most powerful empires in the world, but then it quickly fell. Was it through civil war? Nope. Nearby enemy tribes realized they had been using caravans to bring in food and supplies, so they stayed far away from the walls and took out the caravans. Rome eventually began to starve and broke out into fights over the last bits left until finally the entire city had died.
Targeting Vegas would be an economical choice and also a casualty choice. A lot of people travel here to gamble and waste millions if not billions of dollars every year. Taking out that system would do tremendous damage to the state of Nevada and would do a bit of damage to the United States' economy as well (after all, those casinos had to pay taxes as well. Now they can't). The amount of nukes targeted at Vegas is yes, absurd, but there's also the fact of people driving in and out of Vegas every day. Those nukes may have also been traveling to hit I-15 and eradicate thousands of lives driving in and out of the city.
Also we see that House, the enigmatic leader of RobCo also based himself here. He alone was able to generate untold amounts of robots for civilian and military purposes, and taking him out would also have a large impact on the United States.