Sense 2.5 is the latest UI from HTC. It was made for the larger WVGA screens but has been ported to fit on our VGA screens. It has alot of cool features, like integrated weather, new stock & Twitter tab, most of the tabs have improved greatly.
Sense 2.1 is similar to 2.5 but uses less memory, but has less features. I like to think of it as a cross between the old manila 2.x & Sense 2.5.
as far as the SYS...
WM 6.1 - the stock SYS
WM 6.5 - just recently officially released
WM 6.5.3 - leaked TEST SYS
21887, 28014 etc are the builds of those SYS'. There's really no place that will tell u the differences, but you will sometimes find new features posted with a new build.
btw....wrong forum