When I researched the areas in Rome before I traveled there I saw many explanations on different areas but really none of them gave me a clear answer about where are the best and most convenient locations to stay at.
So I have prepared a simple but straightforward summary of the areas and best places to stay in Rome.
Let's look at the first map:
With the big circle, I have marked the area where all the main sites are. The arrows indicate the furthest sites you will walk to. Just so you have an understanding of how big this area is:
You can walk from the Colosseum to Popolo Square in about 40 minutes. Of course, I am sure you will stop on the way to see other sites, but the idea is that really within that big circle you can walk everywhere by foot. Rome also offers a great public transport system but I will go into detail about that in a bit.
Then as two separate areas, I marked Trastevere and Vatican. To both, you can easily get to walking while wandering around the city. But if you are staying further away from them and going only purposely there then you might want to consider getting a bus.
So let's look into detail about the best places to stay in Rome:
Without a doubt, the best area to stay in Rome is the one in the purple circle, but also it is very expensive to stay there. If money is not a problem and your main goal is a convenient location then choosing your accommodation within that purple circle will be your best choice. Also, some amazing boutique hotels are located there that can make your trip extra special. If you decide to stay in that area, you pretty much won't need to use public transport or get a taxi at all.
With the yellow circle, I am marking the border where the prices start to get lower but this might require you to take a quick 5-minute bus or taxi drive to the center or specific site you are planning to start your day at. If you are the type of person who walks everywhere. staying within that yellow circle will allow you to get to places walking, but it might be an extra 20 minutes of walking just to get closer to the center.
In green, I marked 2 areas where the prices do start to go down and you can get better value for money accommodations. Also, both are lovely areas by the park so if you do decide to walk everywhere and to the center, you can use the path through the park. So I highlighted these as my top 2 if you are on a budget, that will allow you to stay in a nice area fairly close to the center. Again, the public transport system is great around both areas and you can easily get a bus to Vatican or Trastevere if you wish.
Then Trastevere neighbourhood in blue is an area on its own. It is a cute bohemian area with little streets and loads of lovely restaurants. There isn't much to see, but it is a vibe itself. Also, in this neighborhood, you will be able to find cheaper accommodations than in the center. From there you can easily walk into the center by crossing one of the bridges or take a bus if you are plannign to visit sites further away.
If there is one area to highlight where I wouldn't stay, then it is the one marked in red - the area around the train station. Just from my personal observations. During the day I think it is fine. You have the amazing Santa Maria Maggiore Basilica nearby to see so don't be worried about visiting during the day. Just I don't think I would feel entirely comfortable there going back late to my hotel.
How to get around Rome
As I said Rome is walkable, but if you are staying a bit further away from the center you might consider using public transport. And I do recommend it, as the system is great! Throughout my 5 days in Rome used the bus all the time. I mostly used it in the morning to get into the center or to get to the Vatican and then if I stayed out late for dinner in the center, I then took the bus back to my accommodation.
To understand which bus where I should take I used Google Maps. But they do have city maps in every bus stop so you can also use that option.
You can buy tickets at the bus stop before getting in or if you have a contactless debit/credit card then you can also simply tap it at the little ticket machine on the bus. I would recommend using it only if you have easy access to online banking, so in case a ticket officers get on you can show proof that you paid. Because you do not get a physical ticket if you tap your card on the bus. I was told by locals that it was enough. If you want to be on the safe side then I recommend getting a bus ticket at the bus stop before getting on. All tickets have a set price of around 1.5o Euros. So it does not matter where you go, one price for all routes. The good thing is that one ticket is valid for 100 minutes so if you do need to take 2 buses to get to some specific site, you can use the same ticket.
Rome also has a metro, but as the bus system was so easy and convenient I didn't even try the metro in Rome. If you are planning to use the metro or get a train for some day trips, here is a great local guide that explains more about the public transport system in Rome!