I usually try to work in 1:1 scale, but rarely do I work with formats that large. It's not uncommon for artwork to be set at a smaller scale, though. Here's a question that touches on that: In Illustrator, how do I set my file at 10% scale?
When going back and forth with a customer, I find it easier to communicate with exact sizes. I try and avoid language like "I'd like it 50% bigger" (which is very ambiguous) and rather go for "I set the graphic to be 5 inches wide".
Working in a 1:1 scale saves me the trouble of having to remember to convert the measurements. Illustrator does have size limits, but the dimensions you specified are within the working limits. If you do scale down your artwork, just remember to add a notation somewhere in the file so that it's clear!
If you're concerned about file size, it should not make a significant difference if your artwork is 100% vector.