I can't find the processing fees for the merchants who accept the AmEx GC's so it may depend entirely on your processor's pass-thru fees. Worst case 4%.
I don't worry about multiple cards being used for the same room(s). Most of the time we have couples here and they just have one of them pay using one card. I have had a family group want to each use a separate card for one room. The worst one was a group of 6 in 2 rooms, who had me divide the whole bill and they each paid $48. It takes more time than anything else. The access fee for each dial-in is only 10 cents. The rest of it depends on what kind of rewards card the guest has. But it takes a long time to run 6 cards and keep everyone waiting. It uses a lot of paper and it's very noisy. And someone always has to pee!
Then we get the ones who have 2 paying cash, 1 writing a check and the others using credit cards. So, there is running around for change, running the cards, taking the check. But it is all money and that's what I'm in it for.
If it is 2 or more women I always ask if they want me to split the bill. Many are surprised I will do that but most are happy I will.