This is a great topic. Having inspected hundreds of homes during energy efficiency audits, what I have seen is a lack of air sealing & under/no insulation.
The "Bang for your Buck" improvements usually are:
1: Add more insulation in the attic, it can be stacked on top of existing insulation. Install "wind baffles" & batt insulation near the soffits(4-5'). Loose fill is recommended because batt insulation stacked onto existing insulation can create gaps, causing the insulation performance to drop.
1a. Maybe this should be 1 but...air seal, using low expanding and/or full expanding foam, all plumbing & electrical penetrations before blowing in the loose fill insulation. There is some air sealing with the addition of loose fill insulation, yet this method will ensure an effective performance.
2: The HVAC duct system & registers have to be air sealed. All the joints should be coated with mastik. This includes the return plenum(s), boot structures & if sheet metal tubes are used instead of flex duct, these seams need mastik as well. Generally, if the insulation on the tubing looks "dirty" it is because the conditioned air is flowing out of the ductwork.
2a. Use low expanding foam between the boot & the floor/wall/ceiling & metal tape from the inside of the boot, wrapping up onto floor/wall/ceiling enough to seal but covered by the grill for a clean finish.
2b. Insulate the outside of the boot when air seal is completed; when not located within a chase/soffit arrangement. Increase the R-value of insulation on the ductwork.
3. Insulate the floor, when accessible. Be sure to use a netting or rods to keep gravity from dropping the batts to the ground. This will cause a wicking effect which would be bad, then finish with a polyethylene (plastic) ground cover.
4. Weather strip and install door sweeps. Weather strip attic & crawlspace hatches. Weather strip any access hatch that is between conditioned & unconditioned space ( as Roy N. properly labeled the "building envelope")
5. (Re)seal windows, especially single pane. *note* Replacing windows is the last thing because they are the most expensive, especially when your R-value increase is only 2-3. It may be recommended, not as an energy efficiency strategy but as a "sound proofing solution" for a noisy area.
6. Insulate every hot water pipe that you can touch. Recirculating pumps, depending on the length of the run(s), can add performance benefits.
7. Air seal the can lights, as they are very "leaky". It is important (fire hazard) to first change the bulbs to cfl/led for lower wattage & less heat. The cost of the bulbs is why this is the last recommendation.
These improvements can be made with or without replacing the furnace system and will increase the performance of the house, improve the indoor air quality (IAQ) and create a more comfortable living space. These are great selling points and may be what separates this home from another.
Happy investing...