I did a fair bit of Hi-Hy research when my sister was shopping for a crossover.
They are great vehicles. Reliability has been very high. The only trouble area I found was in the first part of 2006 (the first year of the Hi-Hy), the under-capacity inverters were used that had a fairly high failure rate. Once higher-capacity inverters were implemented part way through 2006, the issues pretty well vanished.
I haven't heard of any trouble areas in the later generations, aside from a few instances of loosening rear axle shaft bolts, but that has likely been designed-out.
Reliability of Toyota's Hybrid Synergy Drive (HSD) is very high. The high-voltage packs last 150,000+ miles (sometimes 250,000+ miles) in the vast majority of cases. The Power Split Device (PSD) is seamless and long-lasting. Computer systems work flawlessly. Power delivery is very smooth and strong.
In a way, the hybrid all-wheel-drive eliminates the drawbacks of conventional, mechanical/electronic AWD systems, since there is no mechanical drive shaft connection between the front and rear differentials. The rear differential is powered independently by a third electric motor/generator (it also assists with regenerative braking).
Aside from the relatively expensive purchase price, downsides are few. Ownership costs are low (aside from registration and insurance) and ownership experience is very satisfying.
Maintenance/repair costs for hybrids are usually lower than those for conventional autos. The HSD system omits the transmission, starter motor and alternator. Since the regenerative braking does most of the work, the wheel brakes last practically forever. The gasoline engine in the HSD leads an easy life, as it operates at the most efficient speed, is infrequently at idle speed and doesn't need to supply much torque. As a home mechanic, the Toyota hybrids are utterly boring, because they hardly ever need anything (and yes, most services are easy to complete at home).
My sister ended up going with something smaller with a lower MSRP (Mazda CX-5), but a used Highlander Hybrid was strongly in the running.
I drive a second-generation Prius (the Hi-Hy's little cousin) I've had since new and am pretty active in the online communities. Once you own a vehicle with HSD, it's tough to do back to anything else.