If there are many friendly units standing in front of an enemy unit (for example many friendly units in melee around a single enemy unit) that enemy unit is untargetable using Combat Mode, and harmful abilities cannot be cast.
Suggestion: Add a checkbox option for Combat Mode which enables the following behaviour: if the reticle doesn't find an enemy on cast, then fallback on WoW's built in Action Targeting.
It can currently be overcome with Macros, but it would be good if there was an inbuilt solution.