How long you can go between dumps (and water fills) very much depends on your habits in terms of how much water you use, as well as on the tank sizes. I know that may sound rather cliche and unhelpful, but water conservation can go a very long ways towards extending one's time.
Typically the biggest water usage comes from showering and dishwashing. Navy showers are the rule, and using minimal wash and rinse water for dishes (a dishpan helps--for that matter, so does using paper plates and cups). With some care, it would certainly not be outrageous to expect a class C to last a weekend or a few days with two people. Using the campground showers, if there are any, would be a big help.
If you don't do too much to set up camp, unhooking can be very quick and straightforward: unplugging the electric, coiling the cord, retracting any awning, and driving off may be all it takes. Conversely, if you set up a lot of stuff (that may need moving) and hook up the water and sewer and cable TV and hang lights off the awning, it will take rather longer.
I would suggest not eliminating a longer RV than 25' outright, even without a toad, as it won't be significantly harder to find parking for a 30' RV than a 25' RV in most cases. You'd generally need two parking spaces end to end in either case. Maybe occasionally you could get away with a single space with the 25' unit if you could hang the back end several feet over some grass or something, but that's comparatively uncommon to be able to do. Naturally, the larger the RV the more difficult maneuvering in general is and the fewer small campsites you can fit in (which can be a difficulty particularly in some older state parks or other public campgrounds).
Driving a class C is rather like driving a U-Haul with comfortable seats and better visibility. Certainly they're affected by winds and passing trucks, as is any large slab-sided vehicle, and don't handle like a little car, but it's not too daunting with a little practice. Whether your wife would be comfortable or not with driving one I have any way of knowing, of course, since that sort of thing varies a lot from person to person.
How necessary reservations are depends on what part of the country you're in and what time of year it is. Around here in Vermont, they're a good idea during the weekends, and probably less necessary during the week. Getting reservations fairly early for holidays is a good idea if you have some specific place you want to go. I've yet to be completely unable to find someplace fun or nice on short notice, but at popular times it can take awhile to find. I mainly gone to state parks.