Best Rome in 1 day tour.

We only have a couple of days there so we need to be efficient.

There's "quantity" and there's "quality". :O)
What sort of time do you actually have? If you have a couple of days, you don't need or even want to try and cram all the "major" sites into just one. I don't know as that's even reasonably possible, depending on which attractions you wish to cover and in what sort of depth.

But if intent on doing it, this is probably the tour I'd choose:

https://www.walksofitaly.com/rome-tours/rome-in-a-day-tour

I haven't done it myself but this company is very highly rated and their tours are often recommended by RS posters who've taken them. Do be aware that the Vatican Museums are closed on Sundays so I'm sure WOI doesn't even offer this tour on that day.

You could do your own tour in a day, start early, go to the Vatican to see St. Peters, walk down to Castle San Angelo into central Rome and basically do Ricks City walk (spanish steps, Trevi Fountain, Pantheon, Piazza Navona, etc.) then into ancient Rome with the Forum and Colosseum. Stop along the way for coffee and lunch. You could split that into two days as well. You will hit the main sights and could add others as time allows. The Vatican museum would be nice, but would chew up hours, time would be better spent hitting the highlights.

I don't know if it's possible/advisable to really see all the major sites in one day. You may not want to do the Vatican tour as that will take several hours out of your day. You could visit St Peters as mentioned above. Just getting around the city to all the locations is going to take some time. The tour suggested is going to have to be very rushed to get all that in.

Personally I would go for the Ancient Rome tour in the morning and Heart of Italy walk/tour in the evening. The fountains and piazza's are more magical during the evening hours .

Thank You! Even though it wasn't recommended, we will try to do most of the sites in 1 day.

Enjoy your trip! Rome is one of my favorite places in the world.

I took a wonderful tour with Flaminia from Free Walking Tours. She also does a tour of the Vatican museum, the city center and a food tour. Great gal, fun and knowledgable. Feel free to send a PM if you would like her contact info.

I did this approximate itinerary 15 years ago with high school students, then repeated it again in March 2017 (in the rain) with my 75 year-old mother-in-law. It is a full day, but with planning, it can be done.

https://www.ricksteves.com/europe/italy/rome-itinerary
Don't forget to book the early (8:30 AM) Coliseum/Forum ticket and the afternoon (maybe 3:00 pm) Vatican Museums/Sistine Chapel tickets, which will allow you to skip the lines.
Enjoy.

Also, don't forget Rick Steves Audio Europe app has great and free audiotours including Heart of Rome (the Pantheon, Spanish Steps, Trevi Fountain, which you could see at night), the Colloseum, Forum, Vatican, Sistine Chapel, etc. We enjoyed them. I also took Walks of Italy tours in the past, and they were all fabulous.