This is how I did it, right or wrong!
I'd advanced to Act II in the game and had completed numerous side missions in order to get the required skill points for this (It may not take this long - depending on how you play the game).
Upgrade the following skills (when you have the skill points): -
Combat > Improved Focus > Slowed Focus.
Crafted Items > Lure > Focus Boost.
To craft "Focus Boost" You can either scavenge "Pills" from cars you jack (and other random places, "City Hotspots" - if people are being generous!), or buy them from Pharmacy's.
Once you have all of the above I recommend doing a "Criminal Convoy" or "Gang Hideout" mission (You should avoid the killing "Takedown" target however!).
I did this on a Convoy mission - you can block a road off and then wait for enemies to group up.
Make sure you equip "Focus Boost" to your RB. Once enough (4) enemies are in range, enter "Focus Mode" by clicking the Right Stick - go for head shots, keep track of your "Focus" - if/when it's about to run out press RB to get the "Focus Boost" and just go Rambo!
Edit: Of course you can do this using explosives (IED, Grenade, Grenade Launcher) or environmental items.