Going under 300,000 would indeed be detrimental to the city's psyche. I don't think that will happen though. I think the estimates in the 306,000-312,000 range are pretty good ones.
As roger wyoming II pointed out and as many of us know, these drops in certain areas are a transition towards healthier neighborhoods. The city will never be up to 850,000 again and as romantic as that old, dense city sounds, in reality, it was a quite unhealthy density in many ways, with overcrowding in tenements, where multiple families shared an outside toilet for example.
This link
http://stlcin.missouri.org/census/cen_city_comp.cfm shows the gain or loss of each neighborhood from 2000 to 2010. Areas such as Soulard, Lafayette Square and the CWE, all of which have been going through a process of gentrification for a few decades now all showed small gains.
Other relatively stable looking areas such as Shaw, Tower Grove East and South and Compton Heights all showed greater than expected declines. What accounts for these? Again, these areas have all been under a very gradual process of gentrification though many single rehabs over a number of years. In this link
http://stlcin.missouri.org/census/city_d1.cfm we can see significant losses in the under 5 group as well as the 70+ group. I believe a lot of this loss can be attributed to those two groups rather than wholesale abandonment of these areas. Certainly all the areas mentioned above are in much better shape today than 10 or 20 years ago.
One last note of interest is this link
http://stlcin.missouri.org/census/cen_city_comp.cfm Notice that the African-American population is dwindling at a faster rate than the white population, and when compared to the losses by neighborhood, we can gather that a significant portion of that loss is the continued emptying of north St. Louis. Also note the huge percentage gains among Asians and Hispanics. Although their total numbers are rather small in the grand scheme of things, this highlights the importance of attracting more immigrants into the city. Many other cities that showed huge gains in 2010 did so because they were able to attract immigrants in high numbers.
With all this in mind, I think it becomes increasingly obvious and important that the city and region must do a better job at attracting immigrants and if the city is to begin to increase in numbers in any significant way, the north side, much of which has been totally abandoned or left as a no-man's land, must be rebuilt. This is a unique opportunity to also break the historic dividing line along Delmar, bring more integration to the city and bring in significant numbers of people into the largely vacant north.