1. What are you selling? Are you selling physical products or digital products? If you are selling physical products you will need shopping cart software that calculates shipping costs, allows you to update your stock and so forth. With digital products there is no need for shipping and you will have unlimited quantity of products so will not need certain features.
2. Are you selling your own products or someone else's? If you are selling your own products you can get away with a variety of different software packages out there. However, if you would like to sell other people's digital products, then it would be nice if they have the capability to upload and be in charge of their products, and you would simply collect commissions on their sales.
3. What is your budget? E-commerce software ranges from free to several thousand dollars. Figure out what you are willing to pay and then make a list of possible products to choose from that fit into your price range.
4. Can you change the look and feel of your online store? If you are looking to add your own logo and website's feel to your online store, then you will need to buy software that is written in open-source code. You will also need a few HTML skills and access to Dreamweaver or Frontpage in order to make any design changes, or else find out from the company how much they charge to customize the look of your store for you.
5. What payment processor are you using? If you are already using PayPal as your payment processor, be sure that whatever software you buy is already integrated with it.