This was an annoying bug in CS4, in CS5 it's a bit better but it still happens, both on Macs and Windows. It would help if you submit a bug report http://www.adobe.com/support/feature.html. It has been reported before, but the more reports the better the chance that something will be done about it.
I had reports that after the first $.bp() has been reached, the debugger breakpoints start to work again.
Which preferences did you clear? ESTK has its own set, but I'm not sure whether that helps ...
Is breakpoint mean red point in left gutter?
when I want to create breakpoints, always use this.
$.bp( /*statements*/ );
ex). $.bp( i%3 === 0 ); // break if "i" is multiple of 3
Thanks for those tips, Dirk and mg.