I'm not very active on this forum any longer since we no longer live/travel full-time in our RV, but I wanted to jump in and say that my husband works at BBNP and our family lives here in the park at Panther Junction. You've already gotten a lot of great advice in this thread, so I won't bother to repeat much of it.
What I did want to mention is that for a full year the kids and I lived in San Antonio while my husband worked/lived at BBNP. (Obviously, we are all together now.) As you can imagine, there was a lot of back-n-forth between BBNP and SA. We found that the best route was to take US-90 and drop down to the park via US-385 in Marathon. This is the most direct route, and, in my opinion, the most pleasant route. By going I-10 and dropping down at Fort Stockton you get the usual interstate highway experience, but by taking 90 and dropping down at Marathon you get a real feel for what west Texas is really like. This, of course, would mean that you miss the Caverns of Sonora, but you would get the experience of stopping in Langtry at the Judge Roy Bean rest stop, which is a not-to-miss experience in and of itself. My kids love stopping there. Plus, there is a wonderful overlook of the Pecos River on that route.
(By the way, Marathon is pronounced by locals as "Mara-then". Don't ask me why 'cuz I have no idea.)
May I assume from your post that you will be staying in Terlingua at one of the RV resorts? This is a good option, but I wanted to reiterate that we have large RV sites at the Rio Grande Village here in the park. Coming the time of year that you are coming, you shouldn't have any trouble getting a space. Alternatively, Stillwell Ranch, just outside the north park entrance (on US-385) is a popular place for people with large RV's. If you are traveling down to the park from Marathon, this is a natural place to stop and stay.
As for the park itself:
Everything here is measured in B-I-G distances. Don't let the distance factor scare you. *EVERYTHING* is "far away". Haha
As for not-to-miss things in the park itself... you didn't mention how long you are staying here, but I would give it several days at the minimum.
The park can be divided into three different "zones" -- mountains, river, and desert floor:
If you really aren't into hiking, then there really isn't much to do up in the mountain zone, although it is beautiful up there. You can drive up to the Chisos Basin, see the visitor center, walk the Window View Trail (not to be confused with the Window Trail), have lunch at the lodge, and be done. That's an easy day. If you are into hiking, then there are multiple options. The ones not to miss would be the Window Trail and the Lost Mine Trail.
The river zone is the lush area surrounding the Rio Grande River. If you go to the Rio Grande Village area, you can take a dip in the Hot Springs, take the nature boardwalk trail over the river, and drive to the Boquillas Canyon Trail. If you have passports, you can take the rowboat across the Rio Grande then ride a donkey up to the Mexican border town of Boquillas. This makes for a fun afternoon, but make sure to pay attention to when the border crossing is open. You don't want to inadvertently end up spending the night in Boquillas!
The desert floor area is the largest, and in my opinion the highlight of the park. If you are into hiking, the Balanced Rock hike is worthwhile (down Grapevine Hills Road), as is the Santa Elena Canyon Trail. Otherwise, make sure you do the scenic Ross Maxwell Drive down to Castolon (stopping off along the way to see the sights -- Sam Nail Ranch, Homer Wilson Ranch, Sotol Vista, Burro Mesa Pouroff, Mule Ears View Point, and Tuff Canyon), poke around the old settlement of Castolon for a few minutes, then drive to Santa Elena Canyon. This is perhaps the signature sight of BBNP. If you have time and a good high clearance vehicle, drive back on the Old Maverick Road, stopping at Juna's Jacal along the way.
Outside the park, I highly recommend visiting the Terlingua Ghost Town (and having a bite to eat at the Starlight Café) and also going further toward the resort town of Lajitas. There you can meet the famous mayor of Lajitas, the goat named Clay Henry. Just before you enter Lajitas, stop at the Barton Warnock Visitor Center, which is the visitor center for the Big Bend Ranch State Park. I can't give you much information about the state park, but I do know that the visitor center museum is nice, and the scenic drive along the Rio Grande is supposedly one of the best in the country.
Oh, and I thought I'd mention... the new Fossil Bone Exhibit is having the Grand Opening on Saturday, January 14th. If you happen to be here then, feel free to join us!
Please let me know if you have any questions or need assistance. Enjoy your visit!