Transactions have to be done at the common ancestor of the data being modified, so it's best to use them for data that's nearby in the Firebase data tree. You /can/ do a transaction on a large chunk of data (e.g. the entire user list), but the client would need to sync the entire data and there'd be a greater chance of contention.
If you need atomic bidirectional friendships though, you can do it if you structure your data a little differently. To turn a friendship between a pair of users on and off, you could set /friends/user1/user2 to true iff user1 and user2 are friends. Then you can write security rules that are based off of that to allow and deny access to the users' data.