Mecca was for a long time a place where many different people lived, even during The Prophets time. Medina as well. Were these cities blocked off to non-Muslims after Muhammad's death, or was it something enacted during his lifetime? Also, is it a Quranic ruling or is it something decided on by leaders/population.
Yes, it's Qur'anic. Surah 9, verse 28 of the Qur'an says (according to the Sahih International translation):
O you who have believed, indeed the polytheists are unclean, so let them not approach al-Masjid al-Haram after this, their [final] year. And if you fear privation, Allah will enrich you from His bounty if He wills. Indeed, Allah is Knowing and Wise.
Al-Masjid al-Haram is the Grand Mosque of Mecca. Note that in medieval times (and still to this day, according to some) Christians, because of their belief in the Trinity and in particular their belief that Jesus was / is the Son of God, are polytheists and are therefore banned from the Mosque. Eventually the ban was carried over to the entire city, then to al-Masjid an-Nabawi in Medina, then the entirety of Mecca and Medina.
As time went on this ban spread further and further outward from the cities, until covering most of the Arabian Peninsula. This became an issue to conservative Muslims when coalition troops were allowed to build permanent bases on Saudi soil during the Gulf War. Osama Bin Laden's 1996 Fatwa is sometimes known as the "Declaration of War against the Americans Occupying the Land of the Two Holy Places". In it, among his grievances with the Saudi government we find:
... allowing the American to occupy the land of the two Holy Places ...
Later:
The inability of the regime to protect the country, and allowing the enemy of the Ummah – the American crusader forces- to occupy the land for the longest of years.
And:
Clearly after Belief (Imaan) there is no more important duty than pushing the American enemy out of the holy land.
Then:
Under such circumstances, to push the enemy-the greatest Kufr- out of the country is a prime duty. No other duty after Belief is more important than the duty of had . Utmost effort should be made to prepare and instigate the Ummah against the enemy, the American-Israeli alliance- occupying the country of the two Holy Places and the route of the Apostle (Allah’s Blessings and Salutations may be on him) to the Furthest Mosque (Al-Aqsa Mosque).
Etc. You see it's not strictly Mecca and Medina that must be kept sanctified. Eskan Village, King Abdulaziz Air Base and Prince Sultan Air Base (a US military installation until 2003, now Saudi) are all located near Riyadh or further East. Jeddah, in Makkah region, has King Faisal Naval Base, which was used by US forces during the Gulf War.
Exceptions have, and continue to be made for those who have special sanction to be there however, and there are recent (and therefore off-topic) developments that do away with some of the restrictions on non-Muslims.