I've only once bought a European rail ticket from the US, and I managed to do it on the Renfe website (probably beginner's luck). So I'm inexperienced in this matter.
It is frequently stated here that Loco2 sells tickets at the same price as the operating rail companies and without extra fees. Today I went to the Loco2 website before answering a question on the forum, to verify that it handles Spanish rail tickets. I saw something others may want to know about.
The website states prominently that it doesn't add fees (remaining silent on the issue of ticket pricing). I'm in the US, and Loco2.com defaulted to English and prices in US $. The fare from Madrid to Toledo (which doesn't vary) was listed as $16. That seemed just a bit high to me, and also a suspiciously round number. I went to Renfe.com and found the actual fare to be 13.90 euros, or $15.62 at the time I checked the conversion rate. The Loco2 price in US dollars is about 2.5% higher than Renfe.
I was able to change the currency display to euros at the top of the screen, at which point I saw the same 13.90-euro fare given by Renfe. I didn't attempt to purchase the ticket, so I don't know what happens later in the transaction, but it appears it's important for folks in the US to switch the currency to euros if they want to get the best price possible on Loco2.com. The difference is quite small on a single ticket (less than what we usually see with dynamic currency conversion) for a short trip, but it could make a measurable difference to a family of four buying tickets for a longer trip.