The characters are members of an organization (or superteam, or special military force) under the control of the IAEA.
In 1957, the IAEA was established to ensure that atomic energy would be utilized for "peaceful" purposes. The terror of the bomb's use in WWII awakened the world to the threat of a nuclear war. The organization didn't stop the proliferation of nuclear weapons by the Cold War superpowers, but they have been fairly successful at preventing military proliferation by emerging nations and in furthering negotiations between the superpowers. Since the fall of the Soviet Union the mission of the IAEA has become more difficult. Where they could once stand as moderators between the world's nuclear superpowers, they now find themselves attempting to locate "misplaced" materials and weapons. The world would suffer if these weapons ever came into the hands of terrorists or tyrants. It is the PCs responsibility to find the missing materials and prevent it from getting into the wrong hands.
You could also have the PCs be employees of a "Non-Profit Foundation" combatting nuclear proliferation and terrorism. I call this the McGyver option.
Or they could be members of an elite US force (super or otherwise).
It could even be discovered that "nuclear radiation" is in fact a kind of mana which can be used to summon forth the "forces of darkness." This is in addition to its traditional massive destruction capability. (Supernatural option)
Villains in the campaign can range from:
Just an idea.