This may sound obvious but forming your message and putting in front of the right audience makes a big difference.
Are your audience expecting the type of message you are about to send?
What would happen for example if you were to cold call them with the same message?
If you are selling something in this message is it something that all or only some of your audience may be interested in. Remember the golden rule...
"Don't irritate your subscribers!"
If you are considering sending a marketing message to a large number of users is it relevant enough for their interests? If it is only relevant for a small number then you run the risk of burning your list by encouraging your recipients to unsubscribe because they consider your messaged not relevant to their interests. Remember once a user unsubscribe's you cannot legally get them back. You will of course lose an amount of subscribers anyway but there is no sense in pushing them out with off-topic messages. Because it is very easy to reach a wide audience with email it can often be tempting to flood them with messages on the basis that a small percentage will take up the offer. This really is spamming by any other name opt-in list or not and your customers will feel the same way so be careful.
If you feel your list is too generic then why not split them in to groups. Setup different groups for people by different interests or sectors that relate more specifically to certain niches. That way you can target your customers better, get a higher Send to Click ratio and reduce the number of unsubscriptions.