Coverage of Secretary Clinton's remarks just a few minutes ago seem to be playing relatively well, with people pointing out that it's the first time the US has used such harsh language about Egypt.
One thing to keep in mind is that Clinton's comments are aimed not only at Egypt but at other regimes as well. If the U.S. abandons the Mubarak regime too abruptly it would be seen as a sign of no confidence for other Arab governments facing protests. This would limit the U.S.' influence on these issues which may break in the next week or so.
There's been some discussion of Israel's role in the situation, so let me make a two quick points:
1) Regime change will be bad for Israel. The Egyptian public does not generally support good relations with Israel, and any government which represents their interests is likely to take a much firmer line against Israel. This will hurt Israel's relations with Egypt, and will also limit its maneuvering options on Gaza, where Egypt has played a key role in disrupting Hamas and in prisoner swap negotiations.
2) Israel is not the reason the U.S. has been deliberate and cautious in its support for the protesters. The major U.S. priority right now is stability. Egyptian regime change is likely to cause instability in a number of countries in the Middle East but Israel is certainly not one of them. Additionally, while regime change is likely to cause a headache for Israel, it's not likely to cause violence. That is not necessarily the case in other states in the region.