The main difference is that all specialties participating in round 2 recruitment will be organised on a national basis using what is called the national single centre model of recruitment.
It is also of note that some specialties may not enter round 2.
In round 2 you apply to the national vacancy for your specialty and do not need to give any regional preferences, and you will remain in contention for all vacancies available nationally - not just those in the region at which you are to be interviewed.
When giving programme preferences, there will be no restriction on how many you can rank. You can limit your preferences to a particular region, or include any number of programmes available nationally.
It is very difficult to be able to specify which specialty/region combinations will have vacancies and how many will be available. However round 2 will have considerably fewer posts than round 1.
In addition to unfilled posts from round 1, there are usually posts which arise between the end of round 1 and round 2. Even if a specialty filled all their posts in round 1, new posts can become available. The 'Data' section of each specialty's page shows the post numbers available for each region dating back to 2013 (however, this should be treated with caution and no guarantee of future round 2s).
Although most specialties will participate in round 2, some will not. Cardiology have not held a round 2 since 2012 and some smaller specialties may have insufficient posts to stage a second round. As soon as we are aware that a specialty will not be participating this will be made clear on the relevant specialty's 'Interview dates & posts' page; the 'Data' section of each specialty shows round 2 participation in recent years.
Regardless of whether your round 1 application was successful or unsuccessful, you can still make an application in round 2. Recruiters/interviewers will not even know you made an application in round 1, less still its outcome.
One caveat to add here is that, if you accept a post in round 1, then re-apply and go on to accept a second post offer in round 2 (eg accept a LAT in round 1 and an NTN in round 2) it will be necessary to release one of your accepted posts, notify that region, then make arrangements with them regarding working a notice period; although in most cases, provided that you notify them as soon as you accept another offer, this will not be necessary.