When fighting a large group it is best to keep moving about so they do not surround you and attack from more than one side at once. The trick to fighting the group then is to keep your guard up and wait for one of them to attack and counter it. If there are Brutes or Seekers in the group, it gets a bit tougher but the other tips listed here will help. Try to avoid Brutes or Seekers at first and focus on the others.

Use the following trick when you are in a situation where you will have to take on multiple guards, attack with a group (thieves or mercenaries). While your friends are attacking someone, come from behind with your hidden blade and make the kill. Note: This also works with the final battle where many Ezios battle the final Boss, though instead of your hidden blade (because it is never successful), you will need to use your main weapon.