Advice Please: One week in Italy, landing in Rome on April 2nd.

If you haven’t been to Rome I’d suggest just staying there. You only have 7 nights
We stay near Pantheon where you are dead center and can walk pretty much everywhere

You could day trip to Orvieto and/or Ostia Antica

Assisi is too far as a day trip

Florence needs 3 nights especially if you go there on jet lag day

If you really want both Florence and Rome then go directly to Florence on arrival and put all Rome nights at end

Once you decide let us know and we can advise which sights need advanced purchase/reservations

I'd spend the week in Rome, but if you wish to include Florence too, then head there on arrival. That way all your Rome time is together. I don't think you have time for Assisi.
Go download a guide book, stat, good luck!

I'll vote for just staying in Rome, especially as you're flying in and out of there. As Christine said, you only have 7 nights/6 full days to work with (arrival day doesn't count), and there's a TON to see in the Eternal City if what it has to offer is of interest to you. Six days will allow you to delve a little deeper into this very old and interesting city than most first-time visitors allocate time for.

Location: I'd stay in the Pantheon area, as it's about as central as you can get, IMHO. If up for a bit of a splurge (and if they're not completely booked, which they may be) try Hotel Albergo del Senato (https://www.albergodelsenato.it).

A long walk or walk/run, head out to the Appia Antica. While our knees are no longer up for a trot, we trekked a long stretch of the thing and had a ball. Lots to see along the way; some attractions, like the catacombs, do require tickets and/or an escorted tour but you don't need to book in advance.

https://www.parcoappiaantica.it

Another place for a run would be Villa Borghese; the largest public park in Rome. The best art museum, Galleria Borghese, is located at the far east end.

Tickets: you will need advance reservations for the Colosseum, and unless some folks back out of Coopculture tours which include the underground, you'll need to go through a 3rd party to access that section; Coopculture tours are booked up thru the end of April. We can provide some resources if that's on your must-do list, and I'd advise a tour which also includes the Palatine and Forum as well as the Colosseum. If you just want general-entry tickets to the Colosseum and don't care about the underground, then book a timed-entry day + open time slot on the website.

Vatican Museums: buy tickets in advance: they will be timed-entry:
https://www.museivaticani.va/content/museivaticani/en.html
OR there are some 3rd-party tours which have been highly rated by the RS gang who've done them.

Galleria Borghese: advance, timed-entry ticket are mandatory:
https://galleriaborghese.beniculturali.it/en/

Just a start? There are tons of terrific churches to see for free; many are art museums in-and-of themselves!
Oh and sure, if you need a break from Rome then take that day trip (by train) to Orvieto.

You only have 6 full days, so I'd use it all in Rome with maybe a day trip.

All great advice. My hunch was that it didn't make sense to go to Florence (we'll do that next trip!). You all sealed the deal on staying in Rome. So, please do share any additional advice on making the most of our week in Rome, including any day trips. Thanks so much!!!

I think it's hard to beat Orvieto as a day trip. Well, that's not really accurate. Spending two nights there would be better. There are a many really worthwhile sights in Orvieto--far more than one would have any reason to expect in a town of that size (population 20,000). The historic center is lovely, too. Rick covers Orvieto in the full "Italy" book but not in his "Rome" book. At least get hold of an older edition of "Italy" so you can mine it for tips on Orvieto. Check for a used copy online or look in your local library.

I highly recommend Rick's guide to Rome (the full one, not "Pocket Rome") unless you already have another quality book with detailed info on Rome. The "Sightseeing" section in Rick's Rome book is 325 pages long!

An hour from Roma, delightful garden. Makes a good day trip.

https://www.visittivoli.eu/le-ville/villa-d-este&lang=EN

You might consider heading to Orvieto on arrival
It’s a quick train ride, spend 2 nights get over jet lag then back to Rome
Although you could most certainly spend entire time in Rome and leave wanting more!

For quirky you can’t beat the Capuchin Crypt in Rome
http://www.cappucciniviaveneto.it/

TAnother vote for staying in Rome and possibly taking a day trip to Orvietto or if you want a "Pompeii" type experience, Ostia Antica is a 30 minute train ride. As far as accommodations, I'm a big fan of the Hotel Smeraldo (my family will be there again in late April). Last September, my DW and I walked 9 miles in one of our days in Rome (we're late 50 something), so you will have no problems). Im not a runner, but running along the Tiber river might also be a nice option. So much to see and do in Rome, I could spend a month there and not be bored.

Whatever you decide, have a fabulous time.

You can take a train from the airport to Rome’s Termini station and a direct train to Florence’s SM Novella station and sleep in Florence for three nights. I would buy tickets for the Uffizi Gallery ASAP. You also want to visit Accademia to see Michelangelo’s David. Do take Rick Steve’s self-guided walking tours so you don’t miss seeing anything.
From Florence you can take a direct train to Orvieto and leave your bags at the station and explore the highlights there. When you’re done go to Rome and sleep there the next four nights. Make sure you include a day at Vatican City. Rick’s self-guided walks are excellent in Rome too.

hey hey pulps
yes your trip is short but make the best of it.
we loved walking thru campo de fiori market, the small bakeries, butcher shops, watching the "free" entertainment, bring small euros to throw in their buckets, bought my lemoncello for gifts to bring back to US
marketsofrome.com
so fun to roam around and taste whatever they offer in the markets. heard testaccio market is a great place to check out
mercatocentrale.com/ rome near the train staion. walk around thru all shops
withlocals.com
beautiful countryside day trip: castelli romani
30 minute train ride from rome to frascati and your adventure begins with pierpaolo. a ride thru white wine growing vineyards, summer home for the pope and it's gardens, a ride around lake nemi, make sure stop at ceralli.it in frascati. an italian bakery/pizza oven deli with the "best" porchetta. have a sandwich, nonna is 94 and still baking all the goodies inside.
lacucinaitaliana.com/ nonna rosanna pupuzza frascati roma
read up about nonna and her famous buxom cookie from frascati
italymagazine.com/ lake nemi and it's wild berry
known for it's strawberries growing up the hills and a festival is june about everything strawberry.
eatwith.com/ rome
have dinner or lunch in a residents home with others, home cooked meal and lots of talking about here there and everywhere.
so much to see and do, we loved rome. need to go again to do things out of the ordinary, you guys will enjoy
oldfrascati.com
family owned, read all about the headers, 30 minutes by train to frascati and tour picks you up, pick thr tour you want. get out of the hustle and bustle of rome and have fun.
do come back and let us know how your short trip was.
aloha

Since you are interested in food, check into Eating Europe's tours of Trastevere or Testaccio. We enjoyed the evening Trastevere tour earlier this year; it lasted 4+ hours and included stops at a bakery, butcher's shop, street food stand, and a couple of sit-down restaurants. Oh, and gelato! Plenty of food to be your evening meal. We wished we had taken the tour earlier in our trip so we could have returned to one of the restaurants for a full meal. Next time! We found Rome to be a great city for walking.

Hard decision, I know. Staying in Rome is, of course, the easiest. But hubbie and I would split it. We would take the train immediately to Florence. Stay 3 nights, then back to Rome for 4. But we don’t get to Europe often, so if you do then staying one place makes sense and take a couple day trips,

I agree with Dan above, the Travestere Twlight Eating Tour is not to be missed. Here the link.

https://www.eatingeurope.com/rome/twilight-trastevere/

Two things to take into account - the weather and train costs. The forecast for the next 7-10 days is chilly and rainy. I'm in Tuscany now, taking the train from Florence to Rome on April 3. Right now, a ticket Rome/Florence for tomorrow morning is 45E, but for April 5 is 30E Full price for last-minute tickets is 50E