This doesn't seem to be much of an issue in PvE (yet) but in PvP (CtF, at least), there's nothing more annoying than to be chasing down a player and shoot off an attack just to have it hit the zombie who spawned near you instead of the player who's a bit further away but still within your range. So many annoying deaths.
Can we have abilities default to target within your line of sight and only deviate to within its radial range if there's no target within your direct line of sight? This way Vampire McSuckblood can have a few zombies behind his back but fire off a Fatal Burst at Wesley Snipes, whom he's directly facing, but if Vampire McSuckblood is winding his way through the map and happens to pass an opponent - he can still shoot off an attack and have it hit the guy.
Maybe also a bit of extra fine tuning in the gameplay settings menu? Like letting the player choose to have an extra range of default parameters for his attacks: hit nearest/furthest enemy, hit strongest/weakest enemy, hit enemy with most/least HP.
Obviously this wouldn't apply to attacks that are strictly AoE but I think this would be a step in the right direction.