The fact is, unfortunately, there isn't much of a written record about Mecca prior to Islam.

The Islamic claim is that the first house of God (the Kaaba) was established at Mecca, built by Abraham, and that Mecca was founded by descendants of Ishmael. Islamic perspective claims that the Amalekites brought Polytheism and Idolatry back to Mecca and that the Polytheists turned the Kaaba into a shrine for Idols.

The evidence suggests that the Kaaba was originally a pagan shrine to Hubal. Unfortunately, there isn't much evidence to suggest what Hubal really was or where it came from. What can be said is that the Quraysh, the inhabitants of Mecca, were fiercely devoted to the Kaaba and the idols contained within.

The Quraysh were a mercantile tribe, or so tradition says. Mercantile tribes are a common ancestral tradition among Arabs; the Qataris, Kuwaitis, and Emiratis all say the same; and this much is most likely true. The Quraysh specifically though are odd to be both mercantile and the rulers of Mecca because so little evidence of a mercantile Mecca exists.

The Romans had control over the Hejaz since about 100CE, and even Procopius makes no mention of Mecca, the Kaaba, or any trading post. Given the lack of references in otherwise very thorough historical writings, either Greek, Roman, Indian, or Arab, and its terrible location, there is considerable doubt that Mecca was any sort of trading post or pilgrimage site at all.

Obviously Mecca does exist, and the Kaaba existed at some point, but when either the city or the cube appeared is uncertain. But onto the Quraysh...

Given the absence to the contrary, and to answer this question, we should assume that the Quraysh were the original inhabitants of Mecca, the builders of the Kaaba, and thus pretty furiously offended when one of their residents begins to claim that their god, Hubal, was a false god, and that the Kaaba had been built by Allah, the true God.

Medina, on the other hand, and known as Yathrib at the time, was home to three Jewish tribes; Banu Qaynuqa, Banu Qurayza, and Banu Nadir. As Jews, they were more accepting of Monotheism. (That doesn't mean they were all welcoming, however.) There were also Banu Khazraj and Banu Aws, indigenous Arab tribes.

A few years before Mohammad's flight from Mecca, the Khazraj and Aws went to war. The Jewish tribes are said to have helped both sides; Qaynuqa with the Khazraj, and Nadir and Qurayza with the Aws.

Muhammad was invited to Yathrib to broker a peace in this conflict. For political reasons, the tribes put all their faith into Muhammad as a judge, and Muhammad invited all of his followers to Medina. This establishment of a new peace and polity, a new state of Medina, is why Muhammad was accepted there; he had stopped their war and brought them a new order.

Obviously that did not last, but that is an explanation of why there are such big differences between Muhammad's time in Mecca and Medina.

References:

Mecca Trade and the Rise of Islam by Patricia Crone.

In the Shadow of the Sword by Tom Holland.

The sources I have are from Dr. Yasir Qadhi. He gave a very detailed series on the life of the Prophet Mohammed which is really worth checking out. He is an Academic (Ph.D from Yale and everything, albeit in religious studies) and keeps things as Academic as possible, so he's the source I'm using. His series is more of an academic outlook on the traditional sources, so take of that what you will. He says in one of the Episodes that he uses Ibn Ishaaq and Ibn Hisham, and other sources. https://www.youtube.com/playlist?list=PLAEA99D24CA2F9A8F

He brings up that the reason why the people of Madinah were more open to the message was that they had just come out of a civil war (Battle of Bu'ath) and that most of the older generation had died off and the leadership was under the younger generation, who were looking for something knew, unlike the older generation of Makkah, who were already set in their ways. Dr. Yasir Qadhi says:

The city of Yathrib was composed of three main groups of people. Two of whom were Arab, and one large group of Jews. The Arab tribes were the Aws and the Khazraj. And the Jews we will discuss in more detail: Banu Nadir, Banu Qaynuqa the Banu Quraytha. The city had been a flourishing city; relatively modern. And it had one of the only areas in the entire Arab world where there were Jews. So the year that Abu Talib died, the 10th of the dawah, the prophet PBUH met the first group of the people of Yathrib whom would convert to Islam. The main thing that facilitated this conversion was the Battle of Bu'ath. This battle was a civil war between the Aws and the Khazraj. Small things happened between each other and this built up more and more until finally there was a major battle, the Battle of Bu'ath. This battle took place around 4-5 years before the Hijrah, around 3 years before the meeting with the prophet PBUH. Aisha RA said "the day of Bu'ath was a gift by Allah. It was because of Bu'ath their unity had been destroyed; the battle killed the senior members of the Aws and Khazraj. And those that were left were the younger generation who had seen 10 years of blood and war and they are sick of it. So they are wanting something new and something that will give the meaning, purpose and life." Indeed youngsters are easier to change whereas elders are stuck on their ways. There was one senior member left after the battle, Abdullah ibn Ubay ibn Salool. And it was his seniority that gave him arrogance. In terms of rank he was the undisputed leader of Madinah, were it not for Islam. Eventually of course he became the leader of the munaafiqs.

As for Makkah, about it being a trading hub, it was the Prophet's great-grandfather Hashim who tapped into existing trading networks. Hashim came to power and was unhappy at the state of his home. Recall that the well that turned Makkah into a city had been buried before the Khuza'a era. Everyone was starving. The only thing that made Makkah worth having was the religious significance of the Kabah. Hashim saw how his fellow tribesmen were starving despite people coming in from all over Arabia for Hajj pilgrimage and thought that they could trade. He then realized that in order to trade, they needed stuff to trade, so he decided to start 2 caravans a year. 1 in the winter, 1 in the Summer. 1 goes North to Bosra and trades for Roman goods and Persian goods. 1 goes South to Yemen and trades for Indian goods and African goods. Then when Hajj happens they trade with the fellow Arabs. Thus, the Rihlat Ash-shita Was-Sayf was founded, and is mentioned in the Quran, verse 106:2.

Sources: “Seerah of Prophet Muhammed 24 - Planting the Seeds for Yathrib - Yasir Qadhi | February 2012.” YouTube, 11 Aug. 2012, youtu.be/uKbqn5YuOV8.

“Seerah of Prophet Muhammad 5 - Genealogy & Year of the Elephant ~ Dr. Yasir Qadhi | 14th Jan 2015.” YouTube, 24 Jan. 2015, youtu.be/629isa8LujE.