Depends how loudly you want to play. A few years ago I ran some tests with visitors switching between M60s and M2s as mains, with the usual sub/center/surround as well. At low volumes it was actually tough to tell the difference but once you started cranking the volume (eg helicopter crash scene in first Matrix) it got a lot easier.
I don't know of anyone using M5HP's as mains with a sub yet but I bet they would be interestingly close to M60s as long as you crossed over at 80 or higher.
M60ti, VP180, QS8, M2ti, EP500, PC-Plus 20-39
M5HP, M40ti, Sierra-1
LFR1100 active, ADA1500-4 and -8