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In my opinion, as long as they are not FFA networks, 2nd tier does not do any harm to you even if it does not do you any good. However, check out the SE's focus and respectability before submission.
In addition to the regional focus that seoRank brought up, I think the answer to your question depends on a variety of different factors. I'd definitely look at a combination of how much your customers are worth plus how many you get in a day from the big engines.
When it comes to customer worth: if the average lifetime value of your customer is high, you can afford to spend time submitting to second-tier engines because you know one customer can pay you back for that time. If the average lifetime value of your customer is pretty low, it won't be worth it.
Combine that with amount of traffic you're getting: If you're getting 50,000 hits from Google a day, submitting to other engines probably isn't the best use of time. But if you're getting 500 hit a day from Google, you might be able to make a dent with other engines, too.