you can have multiple configurations; in each one you configure the connection options to one database / persistence unit / context.
Of course it doesn't make sense to have more than one driver for one connection.
To answer about advanced use cases like transactions across multiple different datasources you will need to describe much more your environment; Usually you will not define the driver in hibernate's configuration but refer to application server defined datasources.
Please post more questions about Hibernate or JPA in the correct forum
at
http://forum.hibernate.org/viewforum.php?f=1