OK, I've read your other posts over on the other thread, so I know a little more about you. I was going to warn you to take ASA 101 and/or rent some daysailors before buying, but you've already done that, so you're off to a great start.
I love my Catalina 250, and it grows on me every year as I do the little things to make it "my own." I was attracted by many of the same features you are: comfortable cockpit (much roomier than comparably sized Pearson, Hunter, etc.), big enough cabin for the kids or adults to sit comfortably down below if they get bored, tired of being in the cockpit, or too much sun exposure. My wife really wanted a private enclosed head, which made a 25 footer the minimum size that we could consider.
Although Denise encourages you to go a little larger (as she did for me a few years ago), and she has a big-ass O'Day 30 so she "walks the talk"
, I personally wouldn't go too large in the river. The larger the boat, the less nimble it is for tacking, and you will do a lot of tacking in the river. Also, if you rent a slip right in the river (as in Essington), maneuvering in the cross currents will get trickier for a larger, heavier boat. The currents are much less of a factor if you take a mooring, and probably also less of a factor in a place like Winters (though skinny water may get you in trouble there with a larger boat).
The C250 is a nice, modern design that favors creature comforts over performance. The high freeboard provides good interior headroom (almost standing in the wing keel version), but also makes the boat tender. You need to be very attentive to gusts and prepared to reduce sail area earlier than you normally would with other boats. However, it still reaches hull speed pretty easily while reefed.
However, the C250 has many detractors who don't like its sailing characteristics. The prior owner of my boat appeared to be scared to get onto the boat to do the test drive (I still believe that something happened to scare him), and the owner prior to him told me he did not like the way this boat sailed compared to the C30 that he owned previously (I actually called him to get additional history on the boat). Those who like the stability that comes with that "heavy boat feel" will have some adjusting to do with the C250. You can get a little more of that feel with the older, heavier C25. It has a little less freeboard than the C250, so is less tender. You should look at both boats before buying.
You are right to take a slip or mooring instead of trailering. Trailering a sailboat each time you use it almost certainly ruins the fun, especially if you have kids waiting impatiently. The only exception to this would be if you have a place that allows you to store the boat/trailer in their yard with the mast up, so you can leave it rigged.
I'll mention one other nice thing about the C250 that I only came to appreciate when I chartered a C36 last week. Its modified B&R rig has no forward lower shrouds. I believe that his was primarily done to make it easier to trailer (only need to detach the forestay to drop the mast), but it also makes the boat tack much easier (especially with a 110 genoa, and a continuous sheet attached via a cow hitch). The C36 that I chartered last week had a 135 genoa and two separate sheets attached via bowline, and the bulky knots would get caught up in the lower shrouds every time we tacked, often requiring me to go forward to unfoul everything. You will do A LOT of tacking in the river, and the C250's combination of modified B&R rig makes tacking easier, especially if you have a smaller genoa and avoid the use of bowlines to attach the sheets.
I was glad to see that you are not spooked by industry. I'm a chemical engineer, so a chemical plant or two on the river does not really bother me (though I try to avoid Paulsboro if the wind is from the south). There is a lot of interesting stuff that happens on the river, from occasional seaplane landings, ospreys and Ospreys at Boeing, a pretty cool looking series of marinas in Essington, cute waterfront houses in a few locations (Navy Yard, Bridgeton, etc.) It's really not a bad compromise in exchange for the benefit of being so close to home, especially if you're primarily doing daysailing. For cruising, you really have to go all the way to the canal before you have anywhere worth stopping. And you do need to be always vigilant about avoiding the commercial traffic, but I've never found that to be excessive.