>> DIY, do you ever put all your lists together for a mailing or do you always just do focused mailings from lists that match the product?

Definitely!

There's no reason to annoy 95% of a "weight loss" (for example) leads list with a "make money" promo. You're message will not be congruent with what they signed up to hear more about, you'll piss off plenty and you'll simply be pushing a message that doesn't match your crowd.

As often as possible, think about your email marketing as if it were costing you 50 cents to mail to every email address. With THAT in mind (vs. the "just press Send cause it's free!" mentality)... you'll find that you give a lot more thought to which promotion goes to which targetted list and how that message is crafted.

Idealy though, you should be building your leads lists for one industry. but if you ARE in multi niches, do NOT mail every offer to every lead.