One thing that has been happening for me since the release of DF, the “Invalid Target” message occurs rather frequently on newly acquired targets. Typically in a multi-target situation, but occasionally just targeting a fresh mob.
Moving off the target and coming back to it seems to work, but yeah, that’s just awkward, and having to be aware of the issue for every new target is just no bueno.
The little, seemingly inconsequential, bugs like this end up being quite frustrating.
I’m experiencing this as well. As far as I can tell, it only happens if you target the mob involuntarily, for example if it attacks you and you automatically target it. Auto attacks will work in this scenario, but you can’t use any abilities until you target something else and then go back to the original target. It seems to happen much more often on my monk than on my evoker as well.
I found two potential fixes on reddit but haven’t had a chance to try them yet. They are to make sure that “Mouseover Cast” in options->gameplay->combat is completely disabled, and also to make sure “Auto Self Cast” in that same menu is also disabled.
Thanks Taz, I’ll check those settings. And yeah, you are probably right on the auto-target thing.
UPDATE 10.0.5
Bug still present.
Shut all the settings off as suggested by this thread to no avail.
I believe it to be a problem with the Interact key, because it only happens to me when I land somewhere to mine or open a dirt pile and something attacks me. It’s like the interact key wants to target the node and that overrides the fact that my actual target is the mob. I would disable the interact key to test that idea, but I like it too much.
I’d love to get to the bottom of this too because it’s really disrupted my playing rhythm.
The main time it happens is, as most have observed, when you land near a mob and it attacks you first. Have to actively mouse click on it to target it for anything to work, when normally my opener (eg Stormstrike) both targets and attacks.
It also happens when I Overload a Molten node and the fire elemental appears, I have to click it first before any of my spells will target it, whereas normally they automatically target the nearest hostile.
So I suspect it has something to do with the mob targeting you first.
I will test to see if turning off the Interact key changes anything though. If the game comes up again.
I’m having the same issue but It’s when using a game pad and with console port. I’ve noticed at one point it would work but then when I respec It’s broken again! If anyone has a solution to this please let me know! I have really enjoyed playing on a controller!!
I was having this issue when fighting groups of mobs. One mob would die, and then, instead of autotargeting the next and fighting on like it’s always done, I’d be targeted on the next mob but it would say Invalid Target and I’d not be able to use any abilities on it. The only way to “fix” the issue was to actually select the target that I was already focused on, either by clicking on it or tab targeting it. It looked like this:
Clearly, I’d already damaged the next mob with aoe, so how could it be an invalid target? The mob I just killed would have an orange nameplate, as opposed to a grey one, which is also weird.
Solution (for me): It finally occurred to me that I’d recently enabled the Interact key (obviously very handy for the many unreachable nodes and backpacks in this bug filled xpac), and as soon as I turned that off again, the Invalid Target problem disappeared.
I think the issue is because the camera is facing the dead mob, and the Interact function is tied to the camera facing an interactable item/mob/NPC in game.
Still happening to me as well, and confirming that the options I mentioned previously don’t seem to have done anything. Happened enough to annoy me and stick in my memory while I was running Siege of Orgrimmar on my hunter last night. I’ve now disabled the Interact key and I am hoping this fixes it for me as well.
The other thing to consider is action targetting. I never enabled it but it sounds like it works on the same principle as the interact key but for selecting enemies instead of objects. So, if disabling the interact key doesn’t help and you have action targetting enabled, you might consider disabling that, too.
So I wonder if this is somehow in the mix with invalid target as well
Not the focus bits per say, but the “SoftTarget” vars
Pulling at straws, I know 
This sounds like a plausible explanation, and I agree with you on not turning the Interact option off. I find it way too useful in being able to collect all of the ores that spawn inside cliff faces, and are otherwise unreachable when I’m on my gathering toon. Switching it off and on every time I change toons is not an acceptable solution, either, if that is what is actually causing the problem with the mob targetting.
I’m now certain that this problem is caused by the Interact key. I landed to open a dirt pile and got attacked from behind. While facing the dirt pile and with the mob behind me and showing as my target in my target frame, I cast Call Dreadstalkers (which you can normally cast on a target behind you). Got the invalid target error. I spun around so that I was facing the mob and had the dirt pile behind me, and made no other attempts to change my target, and the spell cast as expected. I repeated this scenario a couple more times to be sure, and it always behaved the same.
It seems like the Interact key chooses a target which is both invisible to us and has a higher priority than the target in our target frame. If that is the only way to make the Interact key work, I’m actually fine with that. I’m not exaggerating when I say that the Interact key is my most hoped-for feature in 17 years of playing this game. It works for me dozens of times every day. To me it’s worth the occasional inconvenience. But if it can be fixed so that a hostile target has higher priority than the hidden target, that would be awesome.