Just run across this question, and am surprised that the first example
that came to mind was not mentioned:
Fermat's "Last Theorem" is heuristically true for $n > 3$,
but heuristically false for $n=3$ which is one of the easier
cases to prove.
if $0 < x \leq y < z \in (M/2,M]$ then $|x^n + y^n - z^n| < M^n$.
There are about $cM^3$ candidates $(x,y,z)$ in this range
for some $c>0$ (as it happens $c=7/48$), producing values of
$\Delta := x^n+y^n-z^n$ spread out on
the interval $(-M^n,M^n)$ according to some fixed distribution
$w_n(r) dr$ on $(-1,1)$ scaled by a factor $M^n$ (i.e.,
for any $r_1,r_2$ with $-1 \leq r_1 \leq r_2 \leq 1$
the fraction of $\Delta$ values in $(r_1 M^n, r_2 M^n)$
approaches $\int_{r_1}^{r_2} w_n(r) dr$ as $M \rightarrow \infty$).
This suggests that any given value of $\Delta$, such as $0$,
will arise about $c w_n(0) M^{3-n}$ times. Taking $M=2^k=2,4,8,16,\ldots$
and summing over positive integers $k$ yields a rapidly divergent sum
for $n<3$, a barely divergent one for $n=3$, and a rapidly convergent
sum for $n>3$.
Specifically, we expect the number of solutions of $x^n+y^n=z^n$
with $z \leq M$ to grow as $M^{3-n}$ for $n<3$ (which is true and easy),
to grow as $\log M$ for $n=3$ (which is false), and to be finite for $n>3$
(which is true for relatively prime $x,y,z$ and very hard to prove [Faltings]).
More generally, this kind of analysis suggests that for $m \geq 3$
the equation $x_1^n + x_2^n + \cdots + x_{m-1}^n = x_m^n$
should have lots of solutions for $n<m$,
infinitely but only logarithmically many for $n=m$,
and finitely many for $n>m$. In particular, Euler's conjecture
that there are no solutions for $m=n$ is heuristically false for all $m$.
So far it is known to be false only for $m=4$ and $m=5$.
Generalization in a different direction suggests that any cubic
plane curve $C: P(x,y,z)=0$ should have infinitely many rational points.
This is known to be true for some $C$ and false for others;
and when true the number of points of height up to $M$ grows as
$\log^{r/2} M$ for some integer $r>0$ (the rank of the elliptic curve),
which may equal $2$ as the heuristic predicts but doesn't have to.
The rank is predicted by the celebrated conjecture of Birch and
Swinnerton-Dyer, which in effect refines the heuristic by accounting
for the distribution of values of $P(x,y,z)$ not just
"at the archimedean place" (how big is it?) but also "at finite places"
(is $P$ a multiple of $p^e$?).
The same refinement is available for equations in more variables,
such as Euler's generalization of the Fermat equation;
but this does not change the conclusion (except for equations such as
$x_1^4 + 3 x_2^4 + 9 x_3^4 = 27 x_4^4$,
which have no solutions at all for congruence reasons),
though in the borderline case $m=n$ the expected power of $\log M$ might rise.
Warning: there are subtler obstructions that may prevent a surface from
having rational points even when the heuristic leads us to expect
plentiful solutions and there are no congruence conditions that
contradict this guess. An example is the Cassels-Guy cubic
$5x^3 + 9y^3 + 10z^3 + 12w^3 = 0$, with no nonzero rational solutions
$(x,y,z,w)$:
Cassels, J.W.S, and Guy, M.J.T.:
On the Hasse principle for cubic surfaces,
Mathematika 13 (1966), 111--120.
I don't think that Mertens was unreasonable in making his conjecture. He was a very competent analytic number theorist within the limitations of his time, when the unreliability of computational evidence in analytic number theory was as yet unsuspected. Only with Littlewood's 1914 disproof of $\pi(x) < \mathrm{li}(x)$ did the pitfalls become clear. This inequality had, for the time, superb computational support.
– engelbrekt Jan 16 '10 at 23:30