I use both with different bands, so here's my take:
AC/DC tribute - I'm Angus and need the spread, punch and cut of a 4x12. I need to be the loudest guitar at all times, so a half stack is by far my preferred option. I've gigged with a 2x12 and got away with it, but the 4x12 is SO much better for oomph and projection.
Rock covers - it's a two guitar setup with shared lead and rhythm parts. Balance is important, as is keeping the overall volume manageable. I wouldn't use anything bigger than a 2x12. Martin (from MJW amps) is the other guitarist and he uses a 4x10 or occasionally a 1x12.
As a side note, my 2x12 is semi-open back and works fantastically well in all situations and has plenty of low end etc......
EDIT: Spooky crossed post!