The Colosseum is obviously a must when visiting Italy. The ticket (in June 09) is 12 euros per person which also gives you entry to Palatino in the Roman Forum. Buy the ticket at Palatino where there is no queue, the queues are terrible at the Colosseum.
The forum is free, but it is very interesting visiting teh Palatino.
In all cases this is really not disabled friendly. The forum is flat, but like most of rome uneven. Palatino has many steep steps as does the Colosseum.
All highly recommended.

We arrived at the Colosseum 5 minutes before opening and the lines were already rather long. After going through the mandatory security check, we used our Roma Pass to bypass the line which we felt was very convenient. We listened to the Rick Steves' audio tour (http://www.ricksteves.com/news/travelnews/0602/italy_downloads.htm) and while it was informative we felt it was a bit corny. Overall we enjoyed the Colosseum but felt that the stage, gift shops, sound equipment, etc. took away from the historic feel of the site. We purchased our Roma Pass at the tourist information booth at the FCO airport which we felt was quite convenient. Visit (http://www.roninrome.com/2009/04/27/should-i-buy-a-roma-pass/) for additional information on the Roma Pass.

The Colosseum is certainly a landmark of Rome. Entrance costs €12 (inclusive of Foro Romano and Palatine Hill). I visited it on the 2nd Sunday in May 2009 and surprisingly, the queues were not long (max 5 minutes) in the morning (9am) and late afternoon (3pm). The audio guide costs €4.50. I would recommend you to bring earphones along so that you can plug them into the audio guide and hear better (or even share with your partner). However, when inside the Colosseum bookshop, I saw a Colosseum guide on sale for €4, which I think is a better alternative compared to the audio guide.
One disappointment is that you only get to walk around the arena. I was hoping for some underground passages that we get to walk through.

1) Licensed tour guides with clearly-displayed badges will give you an informative and interesting tour. You will bypass the line entirely, not waiting more than it takes to round up 10 or so people. I highly suggest going on a tour rather than staring into a guidebook because you can soak up your surroundings while appreciating its significance.

2) Steer clear of the gladiator-costumed men. When you see them smiling with a tourist, what you don't know is 5 minutes from now when you're off somewhere else, that tourist is miserable and trying to keep from being completely ripped off. Unfortunately there are a lot of people in this trade in Italy, and as long as there's willing participants, it's not going away anytime soon.

3) If you are going to use the Metro at all in Rome, there is a stop here. (In general, Rome's subway serves mainly residents, as the lines do not cross into tourist zones because of all the archeological interest).

4) At the end of your visit, check out Palatine Hill next door, the 'originial Beverly Hills' of ancient Rome.

5) If you're dying for some lunch, just keep this in mind: if you are walking around the big tourist areas, and spot a huge menu in 5 different languages guess what: YOU WILL NOT BE EATING GOOD ITALIAN...it will be crappy imitation Italian that no respectable Roman would be caught dead eating. So just in general, the further you walk from the white tennis shoes and fanny packs, the more likely your meal will be delicious and memorable.