Today Crimea held a referendum offering voters the choice of seceding from the Ukraine and seeking annexation by Russia or remaining in the Ukraine with more autonomy. Supposedly 95% voted to leave the Ukraine and join Russia.
What the US should do is stay the heck out of Crimea's business. But what we probably will do is slap all sorts of sanctions on Russia. Kerry has already said that the US and "the international community" will not recognize the Crimean vote for secession and that they are still a part of the Ukraine.
I'm pretty sure the US decided to declare independence from unfair rule one time, and didn't let third parties tell them what to do. Of course, we also had a part of the country wish to leave later, and the existing federal government waged a very bloody civil war to stop it.