@Westitude: First and foremost, the absolute rule of politeness, including the rule of traditional formal etiquette, is that every individual and every couple should be addressed in the way that they themselves prefer. It is not the hostess’s right to choose how to address her guests. Rather, it is her responsibility to find out what is their preferred form of address, and use that. Hence, I strongly recommend that anyone who plans to take on the responsibilities of hostess — including all brides-to-be who aren’t willing or privileged to yield the rights and responsibilities of hostess up to a female relative — start right now, with their Christmas cards still not yet in the trash and the hope alive of finding all their envelopes with their valuable return addresses, and begin keeping a “visiting book” (or spreadsheet, database or iCloud contact list) that records such things as how people represent themselves on their own address-labels. For that matter, every mother of a future bride or future groom should do the same, so that they can help out when the bride and groom ask for their input to the guest-list.
But, it can take some time to gather such a reliable list, so you’ll probably have to guess with a few. That is where etiquette can help out. Fortunately there are some simple rules of traditional formal etiquette that you can lean on.
First, in social situations, given name and surname are NOT used together. The gentleman who is called “Mr John Doe” in business situations so as to eliminate any ambiguity regarding who is being named, in formal social situations is called simply “Mr Doe”, and in informal social situations is called simply “John”. So that simply solves your initial problem: if you want to be egalitarian but formal, refer to the Does as “Mr and Mrs Doe.” If you wish to be informal, refer to them as “John and Jane”.
Second, when an escort card is used properly, the lady’s name alone is written on the card. The card is then placed in an envelope, and the gentleman’s name is written on the envelope. So, again, your problem is solved: “Mr and Mrs John Doe” is not used, just “Mrs Doe” on the inside and “Mr Doe” on the outside. If instead of escort cards (which tell a gentleman whom he is to escort in to dinner and where they are to sit) you were thinking of place cards (which sit above each place setting to tell who is to sit there, and nowadays may tell the servants what entree to serve at that place) then you need one per guest, and the “Mr and Mrs John Doe” problem still does not arise.
Third, if for some unprecedented reason you need to use title, given-name and surname together; and yet do not know what name your guests prefer, the modern norm is to use “Mr John Doe and Ms Jane Doe”. This way, the gentleman goes protectively before the lady as is traditional, but each guest gets his or her own title, given-name and surname all together without anyone else’s name interpolated to interrupt it; and it is precisely the same form that is used if Mr Doe’s wife happens to be named “Ms Smith”.