Umm... Well, I'm of the opinion that a Beanimal overflow is like putting a piece of duct tape over top of a screw to hold two pieces of wood together tighter. So there's that.

But no, I'd have no concerns regarding structural integrity if the holes are properly spaced out and the glass is of the appropriate thickness.

I have similar views of the bean animal as Albert does. I'd use the center hole for the return. I prefer side overflows to center overflows, but as Brad suggested, sometimes your plans change and the side overflow would become viewable.

I would go with it centered and make it external if possible.

I have a 4' 120g . Dual overflows , not in corner & I hate it !
My choice would be corner overflow , run the overflow at 45 degree angle .
Just my $.02

Option 3 is the best.

Thanks for all the replies!

run a herbie, only 3 holes needed including the return, easier to plumb and just as fail safe / quiet