Centro Storico / Duomo is the most convenient base for first-time visitors and sightseeing, with Florence's major historic sights close enough to explore on foot.
Oltrarno / Santo Spirito offers atmosphere and neighbourhood character across the Arno, while remaining practical for reaching the historic centre.
Santa Maria Novella is a useful choice when train convenience matters. San Lorenzo / San Marco combines central access with a practical feel and can suit visitors looking for value.
Santa Croce works well for lively surroundings, restaurants and central walkability. Compare the exact position, evening atmosphere and facilities as carefully as the area name.