Opinion on where to visit.

Since your question is very general, I will give you some initial thoughts. When you have more specific questions within a country, the forum will be able to provide much more helpful answers.

We were in Spain for three weeks last Sept/Oct and really enjoyed our trip. That’s a great time to be there - excellent weather and not overcrowded. You could easily spend all three weeks in Spain. Favorites were Sevilla, Ronda, Toledo, Cordoba, Frigiliana, Madrid, Granada. We only saw a portion of it and would like to return. We didn’t have time for Barcelona, yet.

Italy is my favorite country, and three weeks there will just make you want to return again. Too many favorite cities to mention. There’s a lot of variety within both of those countries - beaches, interesting small towns and large cities. I think Italy tends to be more crowded, and Spain is a little less expensive. Both countries have wonderful food. Check some YouTube videos of places and see what appeals to both of you.

When you’re thinking of transportation costs stacking up when adding countries, personally I think an equal issue is how much time you’re spending to reach a new country. For instance, if you stay just in Spain, you could be in each new town traveling by train or bus by noon if you left after an early breakfast.

It is so vague and general that it is difficult for specific recommendations.
Would I enjoy it as much as the UK and Ireland?
Have no idea. It depends if you are comfortable with a foreign language and a very different culture. It would be more comfortable to return to a known area. Rome can be very intense. It is a terrific place but it is not London. You probably would need a higher degree of flexibility in Italy and Spain than you needed in the British Isles. You should spend some time with some travel DVDs from you local library to see what would appeal to you and your friend. Prague is not convenient to Italy and Spain. I would only do Prague if I was in the Germany and/or Austria area.

Italy is a wonderful place to visit for 3 wks. Views, museums, antiquities, great food all fit perfectly with Italy. I like spain but it pales in comp. to italy.do not .forget to visit the dolomites bef the weathrrnturns to snow, amazing mountains. Ck it all out in Rs guidebk.

We used to travel Europe by rental car as fast and far as we could go. But we saw the light and now travel slower--and better.
We try to travel to cities relatively close together that compliment each other. Like:
London-Paris and maybe Barcelona via fast train.
Munich-innsbruck-Venice
Budapest-Vienna-Prague
Rome-Florence-Venice
We also like to go from such an itinerary to a completely different place by a budget European airline on the way home. Like stopping at Lisbon or Copenhagen or Bergen for a few days. But in October, you won't want to go too far north.

Given the time of year, I would be looking at someplace south vs north i.e Spain/Italy not UK etc

I'd go with a place that's new to you, and either Spain or Italy would be a good choice for the fall. Stick to one in order to maximize your exploring time vs. your moving-around time. Either of those countries can fill many, many months, and they each have a lot of variety. Leave the southern areas till the end of your trip, because the weather will be milder there.

With regards to your question "would I enjoy it as much as the UK and Ireland?", Florence is my #1 and London my #2, because I really love museums, art and churches. Ireland is pretty far down my list. If scenery if most important to you, maybe some smaller towns in Italy. I can't comment, because I haven't been to them. I really enjoyed Spain but Italy is the best.

Italy. It is "more different" from the US than the UK, and what you should experience now while you have time. Start with Venice, Florence, Rome and add on from there.

I'd go with Italy. The weather will be nicer than the British Isles and it will be a new adventure for you.

In addition to Rome, Florence, and Venice, I heartily recommend that you add Naples/Sorrento - with access to Pompeii and the Amalfi Coast - and the Ligure Coast from Genoa to La Spezia - with access to Cinque Terre and Portofino. Also, Pisa is a fun stop on the way to or from Florence.

If you're into mountains and have the time, I would definitely recommend Valle d'Aosta and/or the Dolomites. Lake Como and Lake Maggiore are great en route stops too, depending on your time availability.

If possible, start in the north and head south. One idea for a suggested itinerary is to start in Milano or Venice and end in Napoli.

I really like northern Italy in October, Rome and further south in November.

Further north will get cold, and stay cold until spring, somewhere in October.

I like Spain in April. The weather is usually good and there are Holy Week and Seville's April Faire to enjoy.

It is tempting to return to places you loved. After we went to Paris in 2013, my husband suggested we go back there in 2015. Well, I had already seen Paris! I had never been to Italy, so that is where we went. Rome, the Amalfi Coast, Pompeii, Naples--- it was wonderful. We returned to Italy this late April/ early May to Venice, the Cinque Terre, and Lake Como. Like others who have posted, Italy is our absolute favorite place. ( Until we discover other favorite places.) I would encourage you to look beyond places you have been and explore other wonderous places---like Italy! Check RS's Italy book out of the library and find places that intrigue you.