The border crossing with Turkey (between Antakya and Aleppo) is the smoothest place to cross from our experiences and our discussions with other travelers. You’d have to take a bus from Istanbul to eastern Turkey and you can cross the border there. Supposedly there was a train, but it was more complicated. The bus system in Turkey is very good, so that would be far easier. The Syrian visas are cheap and available at the border (for citizens of most countries) or you can get them in advance for slightly more money. The official statement from the Syrian government is that you must have a visa before you arrive, but unofficially they will give you one at the border. We did this and so have many others. You may have to wait several hours at the border while they process you, however. Have a great trip!