Absolutely! Madrid, Valencia, and Barcelona are vibrant cities in Spain with plenty to offer.

Best Time to Visit:
The best time to visit Spain is typically in the spring (March to May) or during the fall (September to November). During these times, the weather is comfortable and the tourist crowds are smaller.

Route and Accessibility:
All these three cities are well connected by Spain's high-speed rail network, AVE, as well as regular flights. You can start with Madrid, then proceed to Valencia, and finally, end your trip in Barcelona.

Altitude and Acclimatization:
Altitude is not an issue as all cities are near sea level. Hence, no acclimatization is needed.

Accommodation and Booking:
Booking in advance is recommended for better deals, especially during peak tourist seasons. A wide range of accommodations from budget hostel to luxury hotels are available in these cities.

Clothing and Essentials:
Clothing depends on the season of your visit. During spring and fall, light to medium-weight clothing is recommended. Always carry a good pair of walking shoes, as these cities are best explored on foot. Don't forget to pack a sun hat, sunscreen lotion, and sunglasses for protection from the sun.

Health and Safety:
Spain is generally a safe country, but take basic precautions like securing your belongings, staying careful in crowded places to avoid pickpockets. If you have any specific medical needs, ensure to carry prescribed medication with you.

Local Etiquette and Respect:
Spanish people appreciate it when tourists make an effort to speak some Spanish. Remember it's customary to greet people with a kiss on both cheeks. Tipping is not mandatory but is appreciated in restaurants. Respect the local culture and tradition, particularly during festivals and public events.