Maximo Roma - making the most of 48 hours

Fly overnight (save a hotel night), SLEEP on the plane, and get going on your first day in Rome - you can start on a Thursday which works out well as all attractions are open and do not have the weekend traffic to deal with.  Having exactly 48 hours, you must be willing to work hard to experience as much of Rome as possible.

Take the train from Leonardo Da Vinci airport to Termini Station, its part of the experience.  It also gets you into the Roma Termini which will get you everywhere you want to go, a cab ride from airport  will cost you about 40 euro, (train was 14 euro ea).

Read a guide book to help you understand a little about the city before going (rick steves italy, or rome were good).

Grab a good guide book and a great pair of walking shoes and you're ready. No need to hire a tour guide unless you want one. You can bypass the lines to the colosseum a few ways. The first is to buy your tickets through the official seller pierreci before leaving home. The second is to buy your tickets to the colosseum/forum/palatine hill combo at the forum or palatine hill entrance. The third is to buy the romapass. All three of these options will allow you to bypass the lines into the colosseum. To bypass the lines to the Vatican museums you can prepurchase them directly through the vatican website. 

There is no need to book a tour of either of these sites unless you want one. With tickets to the Vatican museums you can pick your entry time and spend as much or as little time wandering as you wish. You must pass through the Sistine Chapel in order to exit the museums. After that you can go into the basilica. Day 1 - On the first day you can see ancient Rome by visiting the colosseum, forum, palatine hill, baths of caracalla, circus maximus, Santa Maria in Cosmedin and the Knights of Malta Keyhole. This is a great way to spend the day and see most of the sites if you are on a limitied time allowance.

Day 2 You can take  a 9.00am tour of colosseum/forum followed by a lunch nearby, then walked the city south to circus maximus (could skip this if you are tired), next walk north on Via Cavuto, having a gelato and visiting St Peter in Chains after it re-opens (3pm). This was a nice quiet place and Michaelangelo's Moses is awesome.  Then returned to hotel to unload a couple souveniers), then take the metro to the Spanish Steps and enjoy a walking tour through the Heart of Rome (trevi fountains, piazza navona, pantheon, jewish ghetto) and end with a late dinner in Trestavere - Day 2 will be very long but very wonderful. You could spend 3 weeks or 3 months in Rome, but for 48 hours you can still feel like you make the best of your time and you'll definitely want to return soon.

Have fun.