If you’re flying into Malaga(?) I’d spend a night there to unwind after your fligh and walk around the backstreets, and if you have time the Picasso museum is really good (he was a local).
Seville is a must out of the July/August furnace -there’s just so much colourful life and so many bars and places to eat, you’ll fill your boots there. Two nights.
Barcelona should also be on your list - it’s a great city which suffered in pre-covid times from overexposure that caused a lot of resentment of tourists among the locals. That may have changed now, I don’t know, but architecturally and culturally it’s wonderful.
You shouldn’t miss Grenada and the Alhambra which is breath-taking - you’ll need to book well in advance. That’s another night.
The Basque region is underrated and wonderful but it’s a long time since I was there. San Sebastien is the place to go if I remember (we approached from France via the Pyrenees which was a stunning trip - my dad was adventurous lol).
On that subject, you didn’t say if you’re doing any driving - I’d tactfully suggest to an American not to drive in most European countries especially Portugal/Spain/Italy because I know from experience there are a lot of completely beserk motorway drivers there up your backside at 80mph lights flashing and horns honking when you have a steady stream of cars on your inside lol.
From the North West you can somehow work your way into France and then to Italy.
So skip Bordeaux and also Nice (we were there a only a few years ago - people only rate it because it’s on the Riviera, which itself is overrated and a rip-off for millionaires to pose on their yachts). I’ve heard good things about Lyon (though I’ve never been) and it will give you a taste of central France, and from there to Paris which you really have to do.
Paris is a tiny city by most US city (and London) standards, and you can easily stroll across the centre in an afternoon, so no excuses about not liking crowds lol. @pyatnitski needs to chip in here but my experiences there say definitely skip the Louvre (that really is horribly crowed) but take in Musee D’Orsay if you want a good gallery. Take the metro to the Arab Quarter, Sacre Coeur (great views across the city) and walk through the beautiful streets of Montmartre where Picasso, Apollinaire and Modigliani lived, worked and starved. Eat cheap but delicious merguez and couscous there and soak up the atmosphere.
Most of central Paris I found quite samey after the first couple of times there (central town planning ftl) and probably won’t ever go again. But you must go once.
From Paris you can fly into Florence for a stay and take in other cities but I’d skip Naples. The city’s seen much better days and really only has the stairs that are memorable unless you want to go to Vesuvius and Pompeii (you’d probably have to book well in advance for that too).
If you want the high life then the Amalfi coast will give you plenty (much sooner there than the French Riviera) a taste of it, though I’ve never been.
Special mention also to Sardinia and especially Southern Corsica for peaceful chilling out breaks, my favourite place in the Med. - a stunningly unspoilt haven with bay after bay of soft sand and turquoise sea.
