Every once in a while, the mouse becomes really choppy after I resume the computer from sleep mode. It won't be smooth until I restart my computer and I've had to restart my computer twice today. I don't understand why.
Try to rule out applications. That's to say run only one at a time and see if one app is causing the problem.
I had a similar issue with the Safari 3 beta where after wake up I lost "clickability". I tried running my normal apps minus one at a time till I found out it was Safari/Webkit which was causing the problem. It's fixed now with the new release of Safari.