I have a Kensington Expert Mouse, and everything worked just fine until I installed Trackballworks 1.0.4.
Now, when I click, it normally doesn't register, and when it does it is delayed. When I hold a button down it works every time, but the effect is delayed slightly. Doesn't matter which mouse button, they all do it.
I also ran Fallout 3 to check... exact same problem, but don't see the problem in any other program.

Trackballworks replaced application settings with global settings and according to many Apple boards is a dismal failure that is very difficult to remove due to excessive hidden files. They suggest using Mouseworks instead after you manage to rid your rig of all traces of Trackballworks.