Well, let's look at this a different way and see how many we can pull up before it starts being counterproductive.

Each cast has a 20 second timer.
The window for catching a fish is within 3 seconds of the bobber popping (rough estimate, could be more or less).
The majority of the time, the bobber doesn't pop until the second half of the casting.

Given these parameters, you could argue that 3-4 boxing would be the most fishing that you could do with a standard clicking and rotating client.

Cast on 1.
Wait 5 seconds.
Cast on 2.
Wait 5 seconds.
Cast on 3.
Check bobber on 1, recast.
Cast on 4.
Check bobber on 2, recast.
And so on...

This is some pretty non-stop clicking. I'm not an expert fisher, but I do have a couple toons with it and my highest being 375. I'm just trying to push out some of the common trends that I see.

Another idea would be to find a way to force a cast to go to roughly the same spot every time. I haven't really tried this, but it could be plausable within a few yards of each other. Then, you could hypothetically cast it on all your toons at the same time, wait until a given time and then click across the span of where the bobber could be. This obviously will result in quite a few "Fish got away" and "Nothing on the hook", but if you are doing it with 5-10 toons, it's a small price if it works 60-70% of the time. Less overall clicking and more toons involved, but less of a success rate.

Addons: Anything short of "clicking for you" addons, which are obviously against the ToS, aren't going to really help after a certain number of toons if you plan on a 100% success rate on bobber pops. Flashing the screen might work out, but again, as someone earlier said, it's only a wav file that plays. If their is an event that is triggered, I think it's not accessible for addons. I need to do some digging to see if their is any.

Would be really neat if their was an addon that could bring up a zoom box of the bobber that animates when the bobber moves.

I have been debating about 4 box fishing a lot recently, especially with the significant increase in the stat gains from food buffs. Spending 60-80g on a stack of food is getting a bit out of hand, especially when I am going through a stack every 1-2 days on just my main. (I'm about 400/500 to my 500 Emblems of Heroism achievement. Single-boxed though.)