Frame geometry has the greatest effect on how comfortable, efficient, and responsive a bike will be, but frame materials, wheels, and tires also play a role.
The distance between the front and rear hubs affects how quickly a bike changes direction, how easily it absorbs road shock, and how comfortable it feels. In general, the shorter the wheelbase, the faster the bike turns and the more responsive it is. The longer the wheelbase, the more a bike tends to hold a straight line and the more stable it feels.
The length of the wheelbase also helps to determine how much a frame can flex, which affects rider comfort. A longer frame flexes vertically to absorb shock and provide a comfortable ride over rough surfaces. A shorter wheelbase has less vertical flex, which transmits more shock to the rider and reduces comfort.
Performance road bikes and performance mountain bikes are designed to be responsive and to steer quickly, and usually have shorter wheelbases. Urban bikes, touring bikes, and entry-level mountain bikes are designed to be comfortable and stable, and usually have longer wheelbases.
Chainstays are the frame tubes that connect the cranks to the rear hub. They form the main axis for power transmission to the rear wheel. Short chainstays don't have much sideways flex, so less energy is lost to frame movement while pedaling. Bikes with short chainstays usually climb and accelerate well. However, short chainstays place the rear wheel beneath the saddle, so road shock is transmitted to the rider. This isn't a problem for two to four hour rides on smooth roads, but it can be uncomfortable on longer rides, or off-road. Short chainstays (roughly 1cm of clearance between the rear tire and seat tube) are found on performance road bikes and performance mountain bikes.
Long chainstays place reduce the amount of shock transferred to the saddle. They reduce the sideways angle that the chain takes on extreme ratios (big chainring/big sprocket, small chainring/small sprocket), and reduce friction and wear in the drivetrain. They allow pannier racks to be mounted ahead of the rear hub, which improves weight distribution and stability. Long chainstays (2 to 4cm of clearance) are found on urban bikes, touring bikes, and entry-level mountain bikes.
This is the angle between the frame's head tube (the tube that holds the fork) and the toptube. The shallower the head angle, the more the bike will steer in a straight line. The steeper the angle, the more quickly the bike changes direction. Shallow head angles also place the bike's fork at a shallower angle to the ground, which allows it to flex more and to absorb shock more easily.
Touring bikes and mountain bikes usually have shallow head angles. Touring cyclists rarely need to change direction quickly, so they benefit from a comfortable ride. Mountain bikers also benefit from slower steering, since quick steering reduces control over rough surfaces, and can cause the bike to steer off the ideal line on a trail.
Performance road bikes and racing bikes usually have steep head angles. The ability to change direction quickly is important while racing or riding in a group of riders, and adds to the responsive feel of these bikes.
As a wheel rolls along a road or trail, it meets resistance in the form of small obstructions (bumps, cracks, rocks), as well as energy loss due to friction on the road surface. This is called rolling resistance, and is affected by wheel diameter, tire section, air pressure, and tread pattern.
Imagine your bike has wheels one inch in diameter. A wheel this small isn't much bigger than most of the things that it rolls over, so a lot of energy is lost as it bumps into, up, and over them. Now imagine your bike has wheels that are ten feet in diameter. These wheels would lose very little energy to rolling resistance. In general, large-diameter wheels (700C, 26, 27, or 29in.) can steamroll over obstructions, and have less rolling resistance than small-diameter wheels (20 or 24in.).