I exclude canada and us, focusing only on latin america...
Safety: road conditions are generally ok in Central & South America. You will catch up with driving style.
Where you have to take precautions:
- north border of mexico (with us)
- guatemala, honduras, nicaragua, certain parts of panama
- south america: chile, argentina, bolivia should be fine. certain areas of colombia/ecuador/peru can be dangerous, however, along the panamericana it is quite safe. we cycled and had no problem at all. big cities, coastal areas are generally less safe than mountain areas. but you just have to read travel advice on wikitravel, fco.gov.uk, travel.state.gov. By appropriate preparation, etc, you should be safe.
note: there are many cyclists who do the same route without any problem. so, with a car, you should be fine too.
best route: along panamericana, with some detours/side trips. you will learn a lot as you go, so no need for extra preparation.
motorbike/bicycle websites/forums are also a good source.
this is from a cyclist couple: www.hobobiker.com - with excellent route info
latin america has a lot of small hotels, a lot with secure car parking area. on an average, you will spend app $10 per night. mexico, chile, argentina are more expensive. central america, colombia, ecuador, peru, bolivia cheaper.
food is available in small towns and along the road as well.
fuel, highway tall: prices vary a lot, availability of good fuel, also, however there are a lot of gas stations, especially on the panamericana. highway toll can be just a small fee, or can double your cost of transportation (e.g. in mexico or colombia). but all in all, still cheaper than in north america.
biggest annoyance will probably be: flat tyres. near car repair shops / tyre shops you will have always have to be careful, as they scatter screws and metal pieces to boost their business. but there are plenty of tyre shops along the road. so, even if you have a problem, you can easily get it fixed for a small fee.
timing: try to plan your trip that you reach chile/argentina in the summer (when it's winter on the northen hempisphere: ie nov - feb).
we saw a few of travellers by car, so it is possible. they usually say that border crossing is not so complicated and max you have to pay extra for insurance, etc. no need for carnet douanier.
i am not sure what you can do with the car when you reach argentina. however, we met two guys who bought a van from other travellers and drove it back to north america. so, this could be an option too.
maps: try to get maps for mexico, central america and for the individual countries in south america at home. will be difficult to get a good map later on.
Darien Gap: - as pointed out by others, this is the most challenging part from logistics.
You can ship your vehicle from Panama to Cartagena in Colombia. There are two main ports in Panama. 1) Colon (note it is a very dangerous town!), 2) Almirante
When I was in Almirante, I asked the harbour master and he said theoretically it was possible to ship vehicle from their port too. However, you will have to liaise this directly with the cargo shipping company. Colon is very notorious for being dangerous, but this is where they usually lade vehicles from towards Colombia.
You can not board the ship, so you will have to arrange your own transportation.
a) Cheapest maybe by plane from Panama City to Cartagena (although connections are not the best). Aires is most commonly used.
b) Also cheap but still very beautiful - to fly from Panama City by Panama Air to Puerto Obaldia (app US$80), and take small boat over to Colombia ($12) to Capurgana (visit Sapzurro and beach on panama side - it's amazingly beautiful!), take speed boat from Capurgana to Turbo ($30) and from Turbo to Cartagena by bus (one or two days). I would highly recommend this route, if you want to keep your budget tight.
c) like most travellers take sailing boat (4/5 days - $400) along San Blas Island to Cartagena.
Some links you might find useful:
Have a great trip!