Hmm, well, if the site really has lots of products and some degree of variety than yeah, focusing on one site can not only help an affiliate to focus but also to draw in traffic from a wider demographic. Toys R Us are a crowd puller as it caters easily to kids, parents, teenagers, sportsmen, etc.
Otherwise, ign-up a few programs with complementing products and build a site around it. This is to benefit from cross promotion. The same person might be interested in products from more than one merchant. But of course too much and it gets more complicated and without a right structure and strategy confusing and even distracting for the visitor.
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