Never use third party resellers. They claim to be the 'perfect solution' but booking with the 'national operator' is always the safest.
It is more complicated than that. It depends which route you want to use, how you want to pay and what functionality you want. Some national operators have WWW sites which can be hard to use in English, which might not take the way that you want to pay, or which don't let you pick your seat for a reservation.
For example, Eurostar don't sell Interrail reservations for their trains. Rail Europe do, but have a transaction fee, and didn't take my company credit card, (its registered in Canada). For that transaction
http://www.allaboard.eu/ was better.
For a trip from
Madrid to Lisbon, its best to use Omio as you can do it in one transaction, even if I wouldn't pick them for a UK journey.