If you've done a reasonable job of air sealing and are down to 5ach/50Pa, a simple room-dehumidifier in the basement (set up to drain into a sink-drain or sump) would likely keep up with the whole house that size. You can ventilate with an ERV, but minimize it's duty-cycle in summer for best results. You don't really NEED active ventilation until you get the ach/50 number down to well under 2, or you smoke, etc. You DO have to be consistent about using bathroom & kitchen exhuast fans at the appropriate times, and if you have any atmospheric-drafted gas/propane/oil fired combustion equipement it's important to check for backdrafting potential if you get it that tight.
Keeping the conditioned space air between 40-48% is fine for the shoulder seasons and summer (at 50%+ dust-mites can successfully breed, at 60%+ the mold hazard starts to rise.) But in winter when it's below 50F outside keeping it at 48%/70F means any air-leaks of interior air into wall cavities can condense on the exterior sheathing. If you keep it at 40% that hazard doesn't occur until its under 45F outside. Maintaining it at 30-35% in winter gives you more margin, and is still within the healthy-comfortable 30-50% RH recommended by allergists & other medical types. (ASHRAE says 25-65% is OK.) But as long as the interior wallboard is well sealed everywhere it pretty much won't matter, especially in your climate (or warmer).
In SC air infiltration is likely to be your single largest source of humidity/mold issues once you've reasonably treated the bulk water issues on the perimeter. Removing the humidity from the semi-conditioned basement would be the most-critical, since the air-conditioning on the first floor would keep the joists cooler, potentially below the dew point of the exterior air. Sealing & insulating the foundation sill & band-joist with 1-2" of closed-cell foam would be about right, and limit the edge-zones of the basement-ceiling fiberglass from convecting basement air to the band joist & sub-floor at that critical juncture. If that fiberglass is unfaced on the side facing the basement, it's performance would improve by adding a permeable housewrap as an air barrier.
ECM drives in air handlers weren't news in 1995, but new enough that they'd probably be advertising that fact on the nameplate if it were. You can likely find the specs for the air handler online if you have the model number.
The heating & cooling loads of basements are typically much lower than upper floors, and will be even lower if you insulate the basement. The biggest heat/gain loss factors in walls tend to be the glazed area, and most basements have but a handful of 3-4 square foot windows. Subsoil temps in SC are in the 60s F, so insulating just the walls (not the slab) would give you a decent earth-coupling benefit, where the high thermal mass of the proximate soil can be a benefit for a good fraction of the year. The odds are VERY good that a 3 ton heat pump can handle this "extra" heating & cooling load- it'd probably oversized 2x for a tight 1600' slab-on-grade with an R50 attic, but a Manual-J type heat gain/loss calc would tell. (Solar gains through windows will swamp the attic gains in many houses.) I
In Clemson (and warmer climates) you can go low-cost on basement insulation using 3/8" or 1/4" fan-fold XPS "siding underlayment" against the foundation wall as a vapor retarder against ground moisture, and a 2x4 interior studwall with unfaced batts insulation. (Unfaced insulation and permeable wall finishes are critical, because the foundation needs to dry toward the interior. Foil or kraft facers would be too vapor-retardent, trapping moisture in the studwalls, driving moisture higher in the foundation to potentially rot the foundation sill.) The XPS is to slow down the rate of moisture transfer to the interior enough to keep the studs mold-free, but if there are still bulk-water incursions dripping to the floor behind it, you can still have issues. A sill gasket between the bottom plate and slab as a capillary break is also necessary. If there's any chance of flooding, stopping the insulation a couple feet above the floor might be a good idea, or using 2-3" of un-faced EPS (bead board, like cheap coolers or coffee cups) held in place with furring through-screwed to the foundation, mounting the wallboard to the furring. At 3" of EPS you'd be at the same clear-wall R value as R13 batts in a 24" o.c. studwall, and still semi-permeable enough to let the foundation dry. (If you went with thicker XPS you'd have to stop a 2", and it would be more money, lower R.)
If the structural walls on the first floor are 2x4 construction with R11 batts there may be a comfort & economic argument for beefing that up by blowing cellulose or high-grade super-fine higer density fiberglass (eg JM Spider or Certainteed Optima) in those cavities, which would also help the air-infiltration numbers. (And if it's R8 econo-batts or empty cavites it's a no-brainer- insulating the walls would be a HUGE boost in summer/winter comfort.) It's often possible to blow insulation in without removing the existing batts or ripping open the wall- let the professionals assess what is/isn't possible.
If the windows are in good shape, and seal resonably, etc, fitting them with decent exterior storm windows would be the most cost-effective method of boosting their thermal performance. Only when heavily subsidized does replacing them with an Energy Star or better window make sense on the pure economics, but from a comfort POV newer windows are better than a set of storms.
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