I'm 100 hours into the game and never once used reflex mode (or visible markers actually). It's probably harder but I really don't miss it. Not having reflex mode or the white indicators on screen makes you a lot more aware of your surroundings and teaches you to become a better player.
You still have a couple of seconds to cancel an alert even without reflex mode.
I didn't even think to turn off the enemy markers, damn. That could be fun!