Hi Fletch ... If you limit yourself to just one week, I'd pick Europe and spend the entire week in a world class city ... like Rome, Paris or London. They all have plenty of sights to easily occupy you for an entire week.
And buy or save FF miles so you can go Business Class ... the time lag hits hard on the first day so you need space to rest, and the lounges are great if there are delays. Unfortunately, UA just raised their biz class to 105,000 FF per seat (from 80,000). There are other combinations too, such as upgrading paid economy seats using FF miles - call UA to find out how. Generally, it's not the best way to use FF miles but for a special event it's ok. Or you could purchase one seat and use 105,000 FF miles for the other ... but biz class tabs are high. You can buy up to 60,000 FF miles a year for $1970 - spouse may be able to buy some too and combine. Can't imagine me in economy seats for that long a flight.
Of the three places I've mentioned...I'd take Rome first for the history, art, religion, FOOD, and fun. Grand Flora is a great location if you have pull to get in there.
If it's a romance trip, Paris is great too ... the Champs Elysees site is the one I'd take -- right in the middle of everything. London's County Hall is the best location in London for first timers ... right on the Thames, London Eye, Big Ben, etc. etc....they do speak a form of English there - Rome has a lot of English (even on menus) spoken, and the French won't. I wouldn't make it too late in the year for any of them as they do have a winter there that's cooler than Orlando...Sept/Oct are great months.
Have a great adventure.
Brian