I've been running osCommerce for 12 years now, and I've been through one complete rebuild of the site. It's always been a horrendous pain to work with, requiring lots of PHP work to get add-ons to work together that ought to be standard. Things like the ability to check out as a guest, or to have quantity price breaks, discount coupons, and an order editor aren't standard and don't work well together. Making it look good is even harder.
I'd like to get out of that completely and use a more polished system, ideally one that someone else would maintain. The options I've looked at seem to fall into three categories: Expensive systems for retailers much larger than us; overly simplistic "my first online store" packages with little opportunity for customization beyond appearance; and osC itself and derivatives like Zen Cart.
I've got a totally custom back-end system for printing shipping labels and generating customs forms and handling other workflow tasks and nothing I can afford is likely to come close to what I have there, so I don't need that in the system itself – just the ability to access the order database directly from my system.
I need quantity price breaks, discount codes, ideally per-customer pricing for resellers as well, reliable domestic and international rate quotes for UPS and USPS, and enough flexibility in customizing the front end that I can do things like add warnings specifically for customers in certain countries about shipping policies.
Or to describe it more briefly: Something like osCommerce but with updates more than once every 7 years, actual documentation, and that doesn't require wading through an unsearchable cesspool of undocumented and out of date add-ons to reach a basic level of usability.