Here are the machine's specs, as reported by EtreCheck: I have observed this over a time frame of almost two weeks now.

running Mac OS X 10.8.4 as well as 10.8.5 (both fresh, clean installs!).

booting any of the OS combinations above from a regular, spinning (and known to be in good working order) Seagate HD, an older but perfectly working 300GB WD VelociRaptor, a spare OCZ Agility 3 SSD, and a brand-spanking new 256GB Samsung 840 Pro SSD.

using the original Radeon 5770, Apple's official 5870 upgrade card, and the nVidia Geforce 660 Ti listed above.

with all 3rd party launch daemons, -agents and login items, aside from those installed by Little Snitch, removed.

The result is the same every time - with Little Snitch installed, the box will freeze up at what seems like random points and times, with the UI of whatever app happens to be running in the foreground at the time freezing (*), and whatever app is clicked thereafter freezing as well until the entire machine locks up, with the dreaded beachball of death spinning endlessly. I've waited up to one hour to see if maybe it could recover from the hang. I have done my best to look through the machine's logs using Console.app, but haven't been able to find anything that would have helped me alleviate the problem.

Little snitch for mac 10.10.5