12 day trip in november

London/Rome, yes. London/one city or area in Spain, yes. London/Spain, no. Spain is a very large country.

It depends to some degree on how much time you want to spend in London, which has enough to keep a person busy for many weeks. How painfully do you want to trim your time in London? Rome will take less time than trying to see several cities in southern Spain, and there will be more flight options. I think the weather is likely to be a bit nicer in southern Spain, though.

Please see the responses to your other post asking almost the same question in the Spain forum (and a forum etiquette suggestion: posting essentially the same thing multiple times in multiple places is frowned upon; if your question involves more than one country it's usually best to post in the General Europe forum).

To answer your question: With the limited time you have (and with kids), in November (short days, maybe marginal weather), someplace in "Spain" isn't a bad choice. What would be a bad choice is to try and do a whole country of Spain, which you don't have time for.

So, good to think of "destinations" rather than countries.

London + Madrid, fine. London + Barcelona, sure. London + Seville, yes. But not London+Madrid+Barcelona+Seville - that's too much for the time you have.

London + one place in Spain (or maybe two close to each other) would be a good choice. You'll get a nice mix of cultures and with any luck you'll get mild or maybe even a little warm weather in Spain.

How much time do you have for this? How many nights do you have between your arrival and departure?
That greatly affects the answer.
And get an "open jaw" flight, into your first location and out of your last, That saves a lot of time and stress.

A classic "two city, compare and contrast" option is London and Paris. This is easy as they are only 2¼ hours apart by train, but two very different places. But you need at least a week to do both.

Hmmm.....
Give pause and consider first determining if one destination offers enough experiences without the need to travel to another.
Too often we create the "need" to justify having more than one destination in order to believe a trip is worthy.
London, with your family ages, offers a wonderful diverse menu of opportunities and ez day trips to fulfill a plethoria of wishes.
Barcelona can do the same, so can Rome. Please examine the need for making multiple stops before believing you must have a multiple destination journey.

Just home from Ireland with 2 teens (13 & 15) it was their 1st European trip. They are not city kids at all and prefer quiet, but have travelled a lot in NA.

They loved Ireland & we covered alot of ground each day from 8-5ish, but they would not have done ok with a tack on to London or another city which we had initially discussed. For us it would have been too much, and by day 10 we dropped Northern Ireland off the list.

Maybe choose a city like Paris as suggested & drop it off if becomes too much? Travelling in November would leave lots of lodging options open. Or book an airbnb that has no fines for cancellation if within 24 hours of arrival.

Good luck deciding! So much to see!