For 99.99% of users, [MENTION=65614]Antman[/MENTION]'s post pretty much summed everything up.
Exactly zero major mechanical problems and lots of people have several hundred thousand miles on early 5th gen models. It's an awesome vehicle that does exactly what I bought it for (kid hauler with limited off road capabilities for a single dad). It's handled lots of situations well beyond my original goals, including offroading in places I never thought I'd be able to take it. If someone runs a redlight and totals my 4Runner I'll be at the dealer looking for another one the next day.
That said, for the OCD types:
Mediocre power, though adequate.
Meh mpg.
No posi rear. Can't get a locker in the SR5.
A 5-speed trans. Hello, 1990 called....
Thin body metal.
Alignment range limited.
Steering wobble. Some people have it.
Entune. Why the 5-10 second delay before startling me with music?
Limited interior color choices.
However, if you want a non-unibody midsized SUV with 4wd, it's the only choice.
All these above, plus a bunch of teeny nit-picks:
A recent thread talked about a rare problem with an upper ball joint clip that rattles. I didn't have this problem.
If you drive on rocks, even 4Lo can seem a little fast. Part is the tendency to upshift too quickly, so manually shifting to 1 usually solves this. If it's still too fast then you're in some serious rocks and a gear swap may be what you need.
The early SR5's (mine) and all Limiteds have really low-hanging plastic trim that tends to snag on things when going off road. I tore off my front lower air dam, and now I remove my running boards and rocker trim before going off road. I occasionally hit my rear bumper and have to pop it back in place. Post-2014 SR5's, all Trails, and all TRD Pro models don't have this problem. Not a problem if you stick to mall parking lots and maintained forest service roads.
No easy way to add front sway bar disconnects.
Very minor annoyance: I opted for the 110v outlet in the center console, not realizing that this eliminated one of the cab 12v outlets, leaving me with only a single 12v outlet. Should be spotted with a test drive and doing a little homework. I simply use a 12v->dual USB splitter, and when my kids are with me I have a 110v->dual USB splitter for their use.