My husband and I (33/31) will spend 15 days(end of May) in Spain and Portugal. We will fly to and from Madrid.
We are planning to drive northwest and then south to Lisbon and then go back to Madrid using other route.

What cities should not be missed?
So far we are planning:
- Madrid
- Valladolid
- Leon
- La Coruna
- Santiago de Compostela
- Vigo
- Oporto
- Fatima
- Lisbon
- Estrela
- Seville
- Cadiz
- Malaga
- Granada

We are also considering a day trip to Tangier (Morocco).

Any suggestion is welcome: restaurants, B&B, hotels, car rental, etc..

Thanks in advance,
Patricia & Andre

Definitely do NOT miss Sintra - just outside Lisbon and easily reached by train or car (and probably bus, though I haven't tried that one yet). Sintra is small, gorgeous, and one of my favorite cities so far in Europe!

Zungos
First of all you are planning an ambitious trip for two weeks, with little time for the main places.
Change Valladolid for Salamanca, miss Vigo, Make it short in Oporto.
Fatima(only if you have a religious interest) and add Cordoba in your way back to Madrid and if possible Toledo, if your time does not allow you then drop Malaga.
Estrella(I don't know the place)
Cadiz short visit. Add Arcos de la frontera between Sevilla and Cadiz or is you are interested in Sherry and horses add Jerez.
Forget the day trip to Tangiers, it is a hassle and you will only visit the ugly part of Marrocco. The best of the area is the coast drive on the Spanish side by between Tarifa and Algeciras.
Regarding restaurants hotels and car rentals I think you should look for comments in the forum there are lots of useful information.

After some research, we already changed our itinerary:
- Madrid
- Segovia/Avila/Salamanca
- Santiago de Compostela
- Viana do Castelo
- Oporto
- Fatima/Batalha/Sitio
- Coimbra/Sintra
- Lisbon
- Estrela
- Seville
- Cadiz
- Malaga
- Granada
- Toledo

All comments and suggestion are appreciated..

Zungos
Sorry to propose less places, but you want to cover too many places in a relatively short time.
keep in mind that you should allow at least 2/3 days for Madrid same for Lisbon and for Sevilla.
Santiago the compostela is a must and so are Granada and Toledo.
Less important will be Cadiz and Malaga.
You can always book the two or three main places and leave the others open.

It's not totally where you are going, it's also when you are going to be in certain cities. If, for example, you plan to visit Santiago on a Saturday you should be sure to attend the 11AM 'Pilgrims Mass at the Basilica.

In Galicia, I would try to stop at the Parador (Conde de Gondomar) in Baiona or at the one in Tuy. Baiona is where Columbus made landfall when he returned from his first Voyage of Discovery. Drive south from Baiona on the coast road and stop at Monte Santa Tecla to see the 300 BC Castrenho vilage. They you have to go toward Tuy for the bridge over to Portugal.

You might also plan stops in Guimaraes (birthplace of modern Portugal) and Braga along the way. Northern Portugal is 'booming' economically because of tax breaks they are giving other EU Countries.

On the way between Lisbon & Sevilla you pass the Spanish City of Huelva and Palos de la frontera, the place from which Columbus sailed on that same Voyage.

Stop at the Santuario de la Virgen del Rocio near Almonte (Huelva). If you are anywhere near Pentecost (May 30) there may be some 'happenings' there. It's on the western edge of la Donana, Europe's largest wildlife refuge.

I agree that you should 'scratch' Tangier from your itinerary.

Althought they are among the most expensive Paradors, the Paradors at Santiago de Compostela, Granada and Leon are historic, well-located and very comfortable. (Book immediately if interested!) We also stayed at the Parador in Avila (trip #1) and Hotel Los Linajes in Segovia (trip #2). The Hotel Lisboa Plaza is quiet, but only one block off Avenida Libertade, Lisbon's "main drag."
We checked out a number of car rental companies and got by far the best deal from Auto Europe.

I hate to be a party pooper---but am I the only one who has noticed that you list at least 14 different destinations for a 15 day trip??

It seems like a Parador Package might suit you. But I think the Hostal de los Reyes Catolicos is overpriced. In Santiago, I prefer Hostal Hogar San Francisco, about 200m from the Basilica but only if the Cotolay room (Room #508, I believe) is available. It's huge, has a full size bath and a large double bed (Queen size?). Cotolay was a Carbonero who helped Francisco de Asis build this Convent. It is still a working Convent (Friars, not Nuns). I have stayed in a standard room there (a bit spartan) and in the Cotolay room (twice). Olga, the 'Day Lady' at the Reception desk can tell you if that room is available.

Another Parador that might interest you is the Parador de Cristobal Colon (AKA Parador de Mazagon). It sits on a bluff overlooking the beach a few miles east of Huelva. In late May, you may even be able to enjoy the beach, although it's a 'hike' down the boardwalk (and steps) from the Parador. But about 150m east of the Parador there's a dirt road down to beach parking.