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What neighborhood is the best to stay in while in Rome, Italy?

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I'm going to be in Rome with my husband for three days in September and I am trying to figure out what neighborhood would be best as a home base while we're touring around the city. We won't have a car so we'd be relying on the bus/metro to get around. I initially thought that staying by the Colosseum would be ideal but I'm not sure if it would be difficult to get to the Vatican City or Trastavere from there. I don't know if I want to stay by the Termini Station but maybe it's the most convenient in terms of travel. Does anyone have any suggestions?

Thanks!

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