I have noticed this since upgrading to Lion.
Many times I accidentally use the pinch to zoom feature on the trackpad for Safari. Safari will zoom in a bit, but then the entire tab becomes frozen. No buttons or hyperlinks work, if you enter a new address into the address bar it will load, but it won't show up, etc. The only solution is to close Safari and reopen it.
Others have reported similar problems here
I have no extensions installed.