Demographic Assimilation: "According to a 2002 Zogby poll, 58% of Mexicans said that the ‘territory of the United States’ southwest rightfully belongs to Mexico.'" Mexico, being a bad neighbor, actively encourages both illegal aliens and Mexican-Americans to have their first loyalty to Mexico. This hasn't been a big issue thus far, but we still have porous borders and there's a genuine danger that Mexico could become a failed state. What if the worst happens and we go from 10-12 million illegals in the United States to 25-40 million packed into the southwestern United States in a relatively short period of time? Demographics are destiny, which is something we taught both Mexico and the Indians the hard way, which is why it's so ironic that we think that same lesson couldn’t ever apply to us.
EMP: There haven't been any high altitude nuclear explosions since 1962; so it's hard to definitively know exactly how much damage a nuke exploding over the center of the United States would cause. A Solar Storm, which could theoretically produce almost the same effect, is even more of an unknown. However, it's entirely possible that a single nuclear bomb or Solar Storm could fry enough electronics to send us all the way back to the Dark Ages in the space of a few heartbeats. Airplanes would drop from the sky, the power grid would go down long term, the Internet would go offline, and nearly all the electronics, computer circuitry, and automobiles people rely on would stop functioning. Millions would die in a few months’ time, economic activity would grind to a halt, and people all across America would get to experience the old school "Oregon Trail" video game in real time.
Nuclear Weapons: There's always a chance that some dictator or religious nut could launch a nuclear weapon at us, but as nukes proliferate to more unstable nations, the chances of terrorists or hostile intelligence agencies sneaking those weapons into the United States will increase dramatically. This will especially be true if Iran gets nukes, because that would undoubtedly inspire Syria, Iraq, Saudi Arabia, Turkey, and Egypt among other nations to also acquire nuclear weapons.
Imagine nuclear weapons going off in LA, DC, NYC, Chicago, Houston, and Philadelphia all in the same day. Millions would be killed, tens of millions would be displaced, it would cost tens of trillions, those cities could be unusable for decades, and it's entirely possible we would likely have NO IDEA who is behind it at first. That would seem to make our porous borders into a high priority problem although you certainly wouldn’t realize it from the lackadaisical approach the Bush and Obama administrations have taken to securing the border.
Biological Weapons: The Black Death killed somewhere between 30%-60% of the population in Europe, smallpox killed roughly 300 million people in the 20th century, and less than a hundred years ago, the Spanish Flu killed somewhere between 50-100 million people. Now consider that there are roughly 20 nations that are believed to have biological weapon programs including Iran, Egypt, Libya, Pakistan, Syria, and North Korea. Put together hostile and/or unstable regimes with access to weaponized biological agents with terrorists (or even environmental extremists who believe the planet is overpopulated) and you have the potential for tens of millions of deaths, nationwide disruptions, and panic that could last for months or even years.