User blog comment:D. Cello/PSN Magazine "AC:Brotherhood" preview!/@comment-1625914-20100602160135

All targets in AC2 died in the respective years, with only suppositions and theories about who killed them.

But the Pope was one of the most respected and documented persons in the world at that time, and we have reports that he got sick, stayed weeks in bed and finally succumbed to a disease with symptons and everything. So, killing Borgia with a Hidden Blade would strafe from the "historical accuracy" the AC Series strives for.