"I was looking at Boppard, but noticed a town like Koblenz is much easier to get 1 direct train to/from the connecting towns."
Your source of information might be weak. What date are you traveling?? Here's what the DB site indicates tomorrow's date for the locations you mention. All are direct / transfer-free trains: board once, get off in Boppard:
FRA airport > Boppard direct at 7:08, 9:24, 11:23, 13:23 etc...
Boppard > Cologne direct at 7:07, 8:12, 9:12, 10:12, 11:12, etc...
If you are already using the DB site, these trains are easier to find if you click "only local transport" when you do your search.
Maybe by "connecting towns" you are referring to towns on the opposite side of the river? After your direct train deposits you in Boppard, a subsequent train trip to Rüdesheim or to Braubach will require a change of train, certainly. But you will not have your luggage with you at that point.
"...am I better off to stay closer to one of the larger towns and just day trip down/up the Rhine?"
Probably not. If you book in Boppard as planned, you aren't going to just stay in town the whole time, right? You're going to day trip down/up the Rhine anyway, I imagine, to take a Rhine cruise, or to visit Rheinfels Castle in St. Goar, Marksburg Castle in Braubach, Bacharach, Rüdesheim, Oberwesel, etc. But as a rule, these day trips will be shorter from Boppard.
If you stay in a larger place like MAINZ, your train trips will definitely much longer. If you stay in KOBLENZ, you'll be closer than from Mainz - and maybe closer than from BOPPARD for one or two of these destinations (like Koblenz > Braubach, only 10 minutes.) It just depends on which towns you plan to visit.
Have a look at the map below. It shows towns, railways, ferry crossings (red) and day cruise stops. Find Koblenz and Boppard. Then look for the places you hope to visit. St. Goar, Oberwesel, Bingen (for your cruise departure) and Bacharach, all good "left-bank" towns to visit, are CLOSER to Boppard than Koblenz by roughly 15 minutes in each direction - so your travel time on a day trip from Boppard saves you roughly 30 minutes.
http://www.loreley-info.com/eng/rhein-rhine/walking-hiking.php
The other thing about staying in Koblenz is that the more desirable old-town zone (near the Deutsches Eck) is a fairly long distance from the train station; stay there and you have a fairly long walk to the station or a bus transfer to make. There are hotels near the Koblenz Hbf station, but most of us would probably that agree that the atmosphere there isn't nearly as nice as the one you'll find in Boppard.
What you don't say is WHEN you plan to travel. In the off-season, Koblenz might be your best choice, simply because the smaller towns, though lively in summer, are not very lively and lots of restaurants and sights are hibernating.