Safe, reliable car with adequate cargo space and good fuel economy

You should be looking at hatchbacks instead of sedans because you want more cargo space.

The Toyota Prius has one of the lowest cost of ownerships of any car. It is super reliable. On my 2005, I didn't even need to replace the brakes until 190k miles. Now it is at 257k miles and the only thing that has broken on it is the A/C and the sun visor. If you get a 2017 or newer model year, you'll get every active safety feature no matter which trim you buy. My 2016 has only had a broken windshield and a few recalls performed. It isn't a performance car, but it wasn't meant to be. The trunk has a lot of room, especially with the back seats down. It has been a Top Safety Pick or Top Safety Pick+ since 2010. I get over 55 MPG in my 2016.

If you want a car that is also fun to drive, the 2014 and newer Mazda3 Hatchback fits all of your priorities. Cost of ownership will be a little more than the Prius, but still cheap. If you can't stand road noise this is not the car for you. It is rated to get 39 MPG on the highway in the hatchback. The Sedan is 40 MPG, but you lose a lot of cargo space. 2017 is when the ride got a little softer without hurting handling.

My last suggestion is the Subaru Crosstrek. This is the best choice if you need AWD. It has decent trunk space, doesn't have the typical Subaru oil consumption problems, and offers a refined ride. It gets 32 MPG combined, so less than the Prius and Mazda3, but more than the Soul.

The Kia Soul is probably not the best choice for you because you want higher MPGs and the combined rating for the Soul is 29 MPG. Also, the trunk space is small behind the 2nd row of seats, so you'll need to put them down to open up the cabin.

May I ask, what year is your Santa Fe Sport? Was it the 2.4L?

Lectrofuel surely got his money's worth out of his Prius; they do tend to soldier on at minimal cost although some other models have low cost to own estimates. I'll add to his excellent suggestions:

Hyundia Elantra GT or Kia Niro or Forte: Since you didn't complain about your Santa Fe, I'll assume you had a reasonably good overall exerience with it. If that is indeed the case, you're likely to have a similar experience with these newer Korean models which all have the 10 year powertrain warranty. Any of these are very good cars but Elantra GT gets the most acolades. The Niro is a strong competitor to the Prius with a number of auto journalist prefering it over the Prius

Honda Fit. As a former owner of a 2011 Fit I can vouch that Fits are among the most reliable, lowest cost to own. As for cargo space and flexiblity it is pretty much the leader of the pack. You will find similar sentiments from most car sites. Drawbacks are ride tends to be a bit rough and loud.

Toyota iM: This model is a bit of a sleeper and seems to be off most people's radar. But it has the Toyota reliablity and comes loaded with standard safety features. Like many Toyota's its fun to drive quotient is on the lower end.

You got great advice above and I have little to add. Just one small correction.

The Subaru Crosstrek just like the rest of the subaru lineup does have oil consuption issues on a small number of their cars. The boards show this time and time again.

For example, here is one where a brand new 2016 is consuming oil. While Subaru is diligent working on trying to reduce the problem their inherent design of the H engine causes this to happen (Porsche's have this issue as well). It is something you may have to live with by checking the oil every 1000 miles with a Subaru but besides that, very little goes wrong. I post a link below to the 2016 issue reported.

https://www.subaruxvforum.com/forum/engine-drivetrain/114057-2016-crosstrek-oil-consumption.html